To address the limitations of traditional adhesive bandages such as poor air permeability,insufficient adaptability,and single function,this study developed a novel liquid bandage using rhubarb and borneol as core raw...To address the limitations of traditional adhesive bandages such as poor air permeability,insufficient adaptability,and single function,this study developed a novel liquid bandage using rhubarb and borneol as core raw materials,polyvinyl butyral as the film-forming matrix,combined with glycerol and diethyl phthalate.The preparation process was optimized via L_(9)(3^(4))orthogonal experiment,with film-forming time,film adhesion,and 24-hour emodin dissolution rate as evaluation indicators to determine the optimal process parameters.The product’s film-forming performance,antibacterial activity,skin safety,and wound healing-promoting effect were systematically investigated.Results showed that the optimal process parameters were:rhubarb extract concentration of 12%,borneol concentration of 1.5%,and film-forming temperature of 45℃.Under these conditions,the product had a film-forming time of 3.2±0.3 min,film adhesion of 3.8±0.2 N,and 24-hour emodin dissolution rate of 86.7±1.6%.Performance evaluation indicated that the product exhibited excellent water resistance,antibacterial activity,hemostatic effect,and high stability.This liquid bandage achieves efficient integration of traditional Chinese medicine efficacy and modern film-forming technology,holding promising application prospects in the field of wound care.展开更多
Borneol,a monoterpenoid alcohol,is used widely,particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine.In order to understand the blood a...Borneol,a monoterpenoid alcohol,is used widely,particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine.In order to understand the blood and brain pharmacokinetics after intravenous,intranasal,or oral administration and to investigate the superiority and feasibility of intranasal administration,a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol.Blood samples and brain were collected from mice at 1,3,5,10,20,30,60,90,and 120 min after intravenous,intranasal,or oral administration of borneol at a dosage of 30.0 mg/kg.Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane.The pharmacokinetic parameters were calculated by the software of Kinetica.The calibration curves were linear in the range of 0.11-84.24 μg/ml and 0.16-63.18 μg/g for borneol in plasma and brain,respectively.The methodological and extraction recoveries were both in the range of 85%-115%.The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD).The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%.The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%.The GC-FID method developed could be applied to determination and pharmacokinetic study.The borneol from injection was distributed and metabolized fast without absorption process.The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability.Nasal administration of borneol was quickly absorbed into the blood and brain,was easy to use and had a greater safety than infection,which makes it worthy of further development as an administration route for encephalopathy treatment.展开更多
The present study collected cerebrospinal fluid samples from the corpus striatum in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain microdialysis technology. Levels of excitatory neurotr...The present study collected cerebrospinal fluid samples from the corpus striatum in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain microdialysis technology. Levels of excitatory neurotransmitters aspartic acid and glutamate, as well as inhibitory neurotransmitters glycine and ^-aminobutyric acid, were measured in samples using reversed-phase high-performance liquid chromatography, phosphate gradient elution, and fluorescence detection. Results showed that concentrations of all four amino acid neurotransmitters significantly increased in the corpus striatum following treatment with borneol or moschus, but effects due to borneol were more significant than moschus. Acorus tatarinowii treatment increased ^-aminobutyric acid expression, but decreased glutamate concentrations. Storax increased aspartic acid concentrations and decreased glycine expression. Results demonstrated that borneol and moschus exhibited significant effects on con amino acid neurotransmitter expression; storax exhibited excitatory effects and acorus tatarinowii resulted in inhibitory effects.展开更多
In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The...In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.展开更多
Hyperforin is an antidepressant drug that has unstable therapeutic effects, due to its poor ability to cross the blood-brain barrier. Borneol and electroacupuncture have both been found to increase the permeability of...Hyperforin is an antidepressant drug that has unstable therapeutic effects, due to its poor ability to cross the blood-brain barrier. Borneol and electroacupuncture have both been found to increase the permeability of the blood-brain barrier. As such, the current study examined the distribution of hyperforin in the rat brain, and the effects on the brain distribution of hyperforin of borneol alone （orally administered）, and borneol combined with electroacupuncture treatment. High-performance liquid chromatography technology and pharmacokinetic analysis revealed that treatment with borneol alone （300, 600 mg/kg） increased peak concentration and the area under the curve for hyperforin in the brain. In addition, the bioavailability of hyperforin in rat brain increased by 42.7%. However, increasing the dose of borneol dose did not appear to increase the distribution of hyperforin in the brain. Importantly, applying electroacupuncture at Baihui （GV 20） or Yamen （GV 15） appeared to enhance the brain-delivery effects of borneol, although this effect was weak. Overall, our results indicated that borneol alone or combined with electroacupuncture can provide promising strategies for brain-targeted delivery in central nervous system therapy.展开更多
Objective： This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administr...Objective： This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and Xingnaojing （XNJ）. Methods： The rats were divided into two groups, ischemia-reperfusion （IR） and sham-operated （SO） rats. Each group contained two subgroups： pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion （MCAO）. The blood samples were collected punc- tually after oral administration and a specific gas chromatographic system-flame ionization detector （GC-FID） method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. Results： After administration of borneol, the maximum plasma concentration （Cmax） and area under the curve （AUC） values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the Cmax and AUC had higher values in the borneol subgroup （P〈0.05）. Conclusions： These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.展开更多
Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. ...Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.展开更多
Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hyp...Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hypoxia,cerebral ischemia and alzheimer’s disease,etc.In the treatment of cerebrovascular diseases,borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs,especially to the brain.The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA(TS IIA),salvianolic acid B(SAB)and ginsenoside Rg1 in FDP.Male healthy Sprague-Dawley(SD)rats were given Danshen extracts,Sanqi extracts(Panax notoginseng saponins)or simultaneously administered Danshen extracts,Sanqi extracts and borneol.Plasma and brain samples were collected at different points in time.The concentration of TS IIA,SAB and Rg1 was determined by UPLC-MS/MS method.The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software.In comparison with Danshen and Sanqi alone,there were significant differences in pharmacokinetic parameters of TS IIA,SAB and Rg1,and the brain distribution of SAB and TS IIA when Danshen,Sanqi and borneol were administrated together.Borneol statistically significant shortened tmax of TS IIA,SAB and Rg1 in plasma and brain,increased the bioavaiability of Rg1,inhibited metabolism of Rg1 and enhanced the transport of TS IIA and SAB to brain.These results indicated that borneol could affect the multiple targets components and produce synergistic effects.Through accelerating the intestinal absorption and brain distribution,borneol caused the effective ingredients of Danshen and Sanqi to play a quicker therapeutic role and improved the therapeutic effect.展开更多
Successful chemotherapy with paclitaxel(PTX)is impeded by multidrug resistance(MDR)in tumor cells.In this study,lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel(BOR/PTX LANs)were prepared to circumve...Successful chemotherapy with paclitaxel(PTX)is impeded by multidrug resistance(MDR)in tumor cells.In this study,lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel(BOR/PTX LANs)were prepared to circumvent MDR in C6 glioma cells.The physiochemical properties including particle size,encapsulation efficiency and morphology were evaluated in vitro.Quantitative and qualitative investigations of cellular uptake were carried out in C6 glioma cells.The cytotoxicity of the BOR/PTX LANs was determined by MTT assay.After that,the tumor targeting was also evaluated in C6 glioma bearing mice by in vivo imaging analysis.BOR/PTX LANs have a higher entrapment efficiency(90.4±1.2%),small particle size(107.5±3.2 nm),narrow distribution(P.I.=0.171±0.02).The cellular uptake of PTX was significantly increased by BOR/PTX LANs compared with paclitaxel loaded lipidalbumin nanoassemblies(PTX LANs)in quantitative research.The result was further confirmed by confocal laser scanning microscopy qualitatively.The cellular uptake was energy-,timeand concentration-dependent,and clathrin-and endosome/lysosome-associated pathways were involved.The BOR/PTX LANs displayed a higher cytotoxicity agaist C6 glioma cells in comparion with PTX LANs and Taxol.Moreover,the encapsulation of BOR in LANs obviously increased the accumulation of the drug in tumor tissues,demonstrating the tumor targeted ability of BOR/PTX LANs.These results indicated that BOR/PTX LANs could overcome MDR by combination of drug delivery systems and P-gp inhibition,and shown the potential for treatment of gliomas.展开更多
The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great cha...The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.展开更多
Stroke is one of the leading causes of disability and death globally.It occurs when a major artery is occluded in the brain and leads to death of cells within the injured tissue.（＋）-Borneol,a simple bicyclic monote...Stroke is one of the leading causes of disability and death globally.It occurs when a major artery is occluded in the brain and leads to death of cells within the injured tissue.（＋）-Borneol,a simple bicyclic monoterpene extracted from traditional Chinese medicine,is widely used in various types of diseases.However,no study has proved the effects of（＋）-borneol on functional recovery from permanent ischemic stroke and the mechanism is still unknown.Here,we report that in the rat model of permanent cerebral ischemia,we found that（＋）-borneol（1.0 mg/kg） significantly ameliorated infarct size and neurological scores via reducing the expression of inducible nitric oxide synthase（iNOS）and tumor necrosis factor-alpha（TNF-α） in a dose dependent manner.Notably,（＋）-borneol showed long-term effects on the improvement of sensorimotor functions in the photothrombotic model of stroke,which decreased the number of foot faults in the grid-walking task and forelimb asymmetry scores in the cylinder task,at least in part through reducing loss of dendritic spines in the length,brunch number and density.These findings suggest that（＋）-borneol could serve as a therapeutic target for ischemic stroke.展开更多
Objective: To explore the effect of Bismuth Subgallate/Borneol (Suile<sup>TM</sup> BSB) healing dressing combined with autologous platelet-rich gel (APG) in the treatment of diabetic foot ulcer (DFU). Meth...Objective: To explore the effect of Bismuth Subgallate/Borneol (Suile<sup>TM</sup> BSB) healing dressing combined with autologous platelet-rich gel (APG) in the treatment of diabetic foot ulcer (DFU). Methods: A total of 120 patients with DFU hospitalized in the Changsha Central Hospital from August 2020 to September 2021 were selected and randomly divided into an experimental group (BSB + APG, n = 60) and a control group (BSB, n = 60) according to random number table method. The total therapeutic effect, healing time, hospital stay, level indexes of various inflammatory factors before and after treatment and ulcer area were observed in the two groups. Results: The total effect of the control group was worse than that of the experimental group, and the data between the two groups were significant (P 0.05);after treatment, the levels of inflammatory factors including WBC, CRP, IL-6 and TNF-α in the control group were higher than those in the experimental group, and there was significant difference between the two groups (P 0.05);after 14 days of treatment, the ulcer area in the control group was larger than that in the experimental group, and the data between the two groups were significant (P Conclusion: BSB combined with APG can achieve better therapeutic effect, reduce the inflammatory reaction of patients, and promote wound healing in the treatment of patients with diabetic foot ulcer.展开更多
In this study, with borneol fragments in the crystallized mother liquor of natural borneol used as the raw materials, supercritical carbon dioxide method is adopted for refining to get high purity borneol. The result ...In this study, with borneol fragments in the crystallized mother liquor of natural borneol used as the raw materials, supercritical carbon dioxide method is adopted for refining to get high purity borneol. The result of the experiment shows that the yield and purity are excellent with an extraction pressure of 11 MPa, an extracting temperature of 40°C, a carbon dioxide flow rate of 25 L·h<sup>-</sup><sup>1</sup> and an extraction time of 20 minutes. After detected by gas chromatography, the purity of the crystallization products could reach 96%.展开更多
A gas chromatography mass spectrometry （GC-MS） method has been developed and fully validated for the simultaneous determination of natural borneol （NB） and its metabolite, camphor, in rat plasma. Following a singl...A gas chromatography mass spectrometry （GC-MS） method has been developed and fully validated for the simultaneous determination of natural borneol （NB） and its metabolite, camphor, in rat plasma. Following a single liquid-liquid extraction, the analytes were separated using an HP-5MS capillary column （0.25 mm ？ 30 m ？ 0.25μm） and analyzed by MS in the selected ion monitoring mode. Selected ion monitor （m/z） of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats.展开更多
BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application o...BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.展开更多
Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying t...Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described. The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced. The application of borneol as a natural ingredient added to functional cosmetics was summarized, and its effects on skin-spot treatment, acne skin care, eczema skin care, skin repair and anti-oxidation were introduced. Finally, the possible problems in the application of borneol in cosmetics were put forward, and the application prospect of borneol in the development of cosmetics was given.展开更多
Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered l...Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described.The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced.The application of borneol as a natural ingredient added to functional cosmetics was summarized,and its effects on skin-spot treatment,acne skin care,eczema skin care,skin repair and anti-oxidation were introduced.Finally,the possible problems in the application of borneol in cosmetics were put forward,and the application prospect of borneol in the development of cosmetics was given。展开更多
Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open or...Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.展开更多
(+)-Borneol,the main component of"Natural Borneol"in the Chinese Pharmacopoeia,is a high-end spice and precious medicine.Plant extraction cannot meet the increasing demand for(+)-borneol,while microbial bios...(+)-Borneol,the main component of"Natural Borneol"in the Chinese Pharmacopoeia,is a high-end spice and precious medicine.Plant extraction cannot meet the increasing demand for(+)-borneol,while microbial biosynthesis offers a sustainable supply route.However,its production was extremely low compared with other monoterpenes,even with extensively optimizing the mevalonate pathway.We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate(BPP),which suffers the side-reaction and the competition from the cellular dephosphorylation process,especially lipid metabolism,thus limiting(+)-borneol synthesis.Here,we systematically optimized the dephosphorylation process by identifying,characterizing phosphatases,and balancing cellular dephosphorylation metabolism.For the first time,we identified two endogenous phosphatases and seven heterologous phosphatases,which significantly increased(+)-borneol production by up to 152%.By engineering BPP dephosphorylation and optimizing the MVA pathway,the production of(+)-borneol was increased by 33.8-fold,which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks,so far the highest reported in the literature.This study showed that rewiring dephosphorylation metabolism was essential for high-level production of(+)-borneol in Saccharomyces cerevisiae,and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.展开更多
As a traditional Chinese medicine(TCM),borneol has shown superior ability for anti-infammatory and analgesic activities when coupled with other active ingredients from ancient times.Furthermore,borneol is believed to ...As a traditional Chinese medicine(TCM),borneol has shown superior ability for anti-infammatory and analgesic activities when coupled with other active ingredients from ancient times.Furthermore,borneol is believed to improve blood concentration and bioavailability of drugs.Thus,it has been paired with various TCM formulas since ancient time.The physiological barriers in human can cause signifcant limitations in drug effciency as the drug is primarily restricted from entering into blood and brain.Borneol has been proven to enhance the permeability of biological barriers such as the blood–brain,transdermal,corneal,and intestinal barriers.Moreover,growing interest has been shown in the drug delivery system design for trans-barrier transport involving borneol.Nano-drug delivery system with increased surface area and improved active sites,has been applied to increase the bioactivity of water insoluble drugs.Nano-drug delivery system has been used to enhance drug effcacy by reducing the time of action as compared to conventional administration approach of TCM formulas.Given its ability to enhance crossbarrier permeation and drug effcacy,borneol has been integrated into TCM formulas of drug delivery system for precise and prolonged targeting at tumor sites.However,the design and preparation of a drug delivery system consisting of borneol still face great challenges.Current research fails to unravel the difference in mechanism of action between nano-drug delivery systems comprised of borneol and conventional drug systems coupled with borneol.Enhanced penetration of borneol in drug delivery system is rarely verifed compared to conventional administration with identical drug formulation consisting of borneol regarding dosage and medical indications.This study outlines the current state of research on the properties,formulation and pharmacological effects of borneol,allowing cross-comparison of borneol coupled with single compound and classical TCM formulas for various medical indications.This study aims to provide insights into the design of borneol-based enhanced cross-barrier delivery drug formulation,and the potential development of nano-drug system for TCM formulas with borneol for enhanced bioavailability.展开更多
文摘To address the limitations of traditional adhesive bandages such as poor air permeability,insufficient adaptability,and single function,this study developed a novel liquid bandage using rhubarb and borneol as core raw materials,polyvinyl butyral as the film-forming matrix,combined with glycerol and diethyl phthalate.The preparation process was optimized via L_(9)(3^(4))orthogonal experiment,with film-forming time,film adhesion,and 24-hour emodin dissolution rate as evaluation indicators to determine the optimal process parameters.The product’s film-forming performance,antibacterial activity,skin safety,and wound healing-promoting effect were systematically investigated.Results showed that the optimal process parameters were:rhubarb extract concentration of 12%,borneol concentration of 1.5%,and film-forming temperature of 45℃.Under these conditions,the product had a film-forming time of 3.2±0.3 min,film adhesion of 3.8±0.2 N,and 24-hour emodin dissolution rate of 86.7±1.6%.Performance evaluation indicated that the product exhibited excellent water resistance,antibacterial activity,hemostatic effect,and high stability.This liquid bandage achieves efficient integration of traditional Chinese medicine efficacy and modern film-forming technology,holding promising application prospects in the field of wound care.
基金Project supported by the Key New Drug Creation and Development Programme of China (No. 2009ZX09502-008)the National Natural Science Foundation of China (No. 81073057)the Innovation Team Development Program of Beijing University of Chinese Medicine (No. 2011-CXTD-13)
文摘Borneol,a monoterpenoid alcohol,is used widely,particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine.In order to understand the blood and brain pharmacokinetics after intravenous,intranasal,or oral administration and to investigate the superiority and feasibility of intranasal administration,a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol.Blood samples and brain were collected from mice at 1,3,5,10,20,30,60,90,and 120 min after intravenous,intranasal,or oral administration of borneol at a dosage of 30.0 mg/kg.Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane.The pharmacokinetic parameters were calculated by the software of Kinetica.The calibration curves were linear in the range of 0.11-84.24 μg/ml and 0.16-63.18 μg/g for borneol in plasma and brain,respectively.The methodological and extraction recoveries were both in the range of 85%-115%.The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD).The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%.The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%.The GC-FID method developed could be applied to determination and pharmacokinetic study.The borneol from injection was distributed and metabolized fast without absorption process.The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability.Nasal administration of borneol was quickly absorbed into the blood and brain,was easy to use and had a greater safety than infection,which makes it worthy of further development as an administration route for encephalopathy treatment.
基金supported by the National Natural Science Foundation of China, No. 81173572
文摘The present study collected cerebrospinal fluid samples from the corpus striatum in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain microdialysis technology. Levels of excitatory neurotransmitters aspartic acid and glutamate, as well as inhibitory neurotransmitters glycine and ^-aminobutyric acid, were measured in samples using reversed-phase high-performance liquid chromatography, phosphate gradient elution, and fluorescence detection. Results showed that concentrations of all four amino acid neurotransmitters significantly increased in the corpus striatum following treatment with borneol or moschus, but effects due to borneol were more significant than moschus. Acorus tatarinowii treatment increased ^-aminobutyric acid expression, but decreased glutamate concentrations. Storax increased aspartic acid concentrations and decreased glycine expression. Results demonstrated that borneol and moschus exhibited significant effects on con amino acid neurotransmitter expression; storax exhibited excitatory effects and acorus tatarinowii resulted in inhibitory effects.
基金supported by the Program from Shanghai Uni-versity of Traditional Chinese Medicine(B201725)
文摘In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.
基金the National Natural Science Foundation of China,No: 81001651Opening Project from Key Laboratory of Integrative Acupuncture and Drugs Constructed by Jiangsu Provincial and Chinese Education Ministry,No: KJA200905
文摘Hyperforin is an antidepressant drug that has unstable therapeutic effects, due to its poor ability to cross the blood-brain barrier. Borneol and electroacupuncture have both been found to increase the permeability of the blood-brain barrier. As such, the current study examined the distribution of hyperforin in the rat brain, and the effects on the brain distribution of hyperforin of borneol alone （orally administered）, and borneol combined with electroacupuncture treatment. High-performance liquid chromatography technology and pharmacokinetic analysis revealed that treatment with borneol alone （300, 600 mg/kg） increased peak concentration and the area under the curve for hyperforin in the brain. In addition, the bioavailability of hyperforin in rat brain increased by 42.7%. However, increasing the dose of borneol dose did not appear to increase the distribution of hyperforin in the brain. Importantly, applying electroacupuncture at Baihui （GV 20） or Yamen （GV 15） appeared to enhance the brain-delivery effects of borneol, although this effect was weak. Overall, our results indicated that borneol alone or combined with electroacupuncture can provide promising strategies for brain-targeted delivery in central nervous system therapy.
基金Project supported by the Innovation Team Development Program of Beijing University of Chinese Medicine(No.2011-CXTD-13)the Independent Project of Beijing University of Chinese Medicine(No.2013-JYBZZ-XS-093)the Technology Major Projects of China(No.2014ZX09301306-008)
文摘Objective： This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and Xingnaojing （XNJ）. Methods： The rats were divided into two groups, ischemia-reperfusion （IR） and sham-operated （SO） rats. Each group contained two subgroups： pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion （MCAO）. The blood samples were collected punc- tually after oral administration and a specific gas chromatographic system-flame ionization detector （GC-FID） method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. Results： After administration of borneol, the maximum plasma concentration （Cmax） and area under the curve （AUC） values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the Cmax and AUC had higher values in the borneol subgroup （P〈0.05）. Conclusions： These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.
基金supported by the National Natural Science Foundation of China (No. 81073057)the Key New Drug Creation and Development Programme of China (Nos. 2009ZX09502-008 and 2009ZX09308-003)the Doctoral Fund of the Ministry of Education of China(No. 20090013110007)
文摘Both geniposide （Ge） and natural borneol （NB） are bioactive substances derived from traditional Chinese herbs. The effect of NB on the pharmacokinetics of Ge in rat via intranasal administration was investigated. The concentrations of Ge in plasma were determined by reversed-phase high-performance liquid chromatography （HPLC） after intranasal administration of Ge （4 mg/kg） alone and combined with different doses （0.08, 0.8, and 8 mg/kg） of NB. The intravenous administration was given as a reference （4 mg/kg of Ge and 8 mg/kg of NB）. Compared with the intravenous administration, the absolute bioavailability of Ge was 76.14% through intranasal administration combined with NB. Compared with the intranasal administration of Ge alone, Ge could be absorbed rapidly in the nasal cavity combined with NB; the peak time of Ge in the plasma became shorter （3-5 min vs. 40 min）; the peak concentration became higher （1.32-4.25 IJg/ml vs. 0.67 ug/ml）; and, the relative bioavailability of Ge combined with NB was 90.3%-237.8%. The enhancing effect was attenuated as the dose of NB decreased. The results indicated that NB can accelerate the absorption of Ge dose-dependently in the nasal cavity.
基金the Natural Science Foundation of Hunan Province(Nos.2017JJ2338 and 2020JJ4860)the National Key Specialty Construction Project of Clinical Pharmacy(No.2013-5).
文摘Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hypoxia,cerebral ischemia and alzheimer’s disease,etc.In the treatment of cerebrovascular diseases,borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs,especially to the brain.The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA(TS IIA),salvianolic acid B(SAB)and ginsenoside Rg1 in FDP.Male healthy Sprague-Dawley(SD)rats were given Danshen extracts,Sanqi extracts(Panax notoginseng saponins)or simultaneously administered Danshen extracts,Sanqi extracts and borneol.Plasma and brain samples were collected at different points in time.The concentration of TS IIA,SAB and Rg1 was determined by UPLC-MS/MS method.The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software.In comparison with Danshen and Sanqi alone,there were significant differences in pharmacokinetic parameters of TS IIA,SAB and Rg1,and the brain distribution of SAB and TS IIA when Danshen,Sanqi and borneol were administrated together.Borneol statistically significant shortened tmax of TS IIA,SAB and Rg1 in plasma and brain,increased the bioavaiability of Rg1,inhibited metabolism of Rg1 and enhanced the transport of TS IIA and SAB to brain.These results indicated that borneol could affect the multiple targets components and produce synergistic effects.Through accelerating the intestinal absorption and brain distribution,borneol caused the effective ingredients of Danshen and Sanqi to play a quicker therapeutic role and improved the therapeutic effect.
文摘Successful chemotherapy with paclitaxel(PTX)is impeded by multidrug resistance(MDR)in tumor cells.In this study,lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel(BOR/PTX LANs)were prepared to circumvent MDR in C6 glioma cells.The physiochemical properties including particle size,encapsulation efficiency and morphology were evaluated in vitro.Quantitative and qualitative investigations of cellular uptake were carried out in C6 glioma cells.The cytotoxicity of the BOR/PTX LANs was determined by MTT assay.After that,the tumor targeting was also evaluated in C6 glioma bearing mice by in vivo imaging analysis.BOR/PTX LANs have a higher entrapment efficiency(90.4±1.2%),small particle size(107.5±3.2 nm),narrow distribution(P.I.=0.171±0.02).The cellular uptake of PTX was significantly increased by BOR/PTX LANs compared with paclitaxel loaded lipidalbumin nanoassemblies(PTX LANs)in quantitative research.The result was further confirmed by confocal laser scanning microscopy qualitatively.The cellular uptake was energy-,timeand concentration-dependent,and clathrin-and endosome/lysosome-associated pathways were involved.The BOR/PTX LANs displayed a higher cytotoxicity agaist C6 glioma cells in comparion with PTX LANs and Taxol.Moreover,the encapsulation of BOR in LANs obviously increased the accumulation of the drug in tumor tissues,demonstrating the tumor targeted ability of BOR/PTX LANs.These results indicated that BOR/PTX LANs could overcome MDR by combination of drug delivery systems and P-gp inhibition,and shown the potential for treatment of gliomas.
基金supported by the Distinguished Professor Project of Liaoning Province.
文摘The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.
基金supported by grants from National Natural Science Foundation of China(91232304, 31530091,81571188 and 81222016)the Natural Science Foundation of Jiangsu Province(BK2011029)Distinguished Young Scientists Fund(BK20130040)
文摘Stroke is one of the leading causes of disability and death globally.It occurs when a major artery is occluded in the brain and leads to death of cells within the injured tissue.（＋）-Borneol,a simple bicyclic monoterpene extracted from traditional Chinese medicine,is widely used in various types of diseases.However,no study has proved the effects of（＋）-borneol on functional recovery from permanent ischemic stroke and the mechanism is still unknown.Here,we report that in the rat model of permanent cerebral ischemia,we found that（＋）-borneol（1.0 mg/kg） significantly ameliorated infarct size and neurological scores via reducing the expression of inducible nitric oxide synthase（iNOS）and tumor necrosis factor-alpha（TNF-α） in a dose dependent manner.Notably,（＋）-borneol showed long-term effects on the improvement of sensorimotor functions in the photothrombotic model of stroke,which decreased the number of foot faults in the grid-walking task and forelimb asymmetry scores in the cylinder task,at least in part through reducing loss of dendritic spines in the length,brunch number and density.These findings suggest that（＋）-borneol could serve as a therapeutic target for ischemic stroke.
文摘Objective: To explore the effect of Bismuth Subgallate/Borneol (Suile<sup>TM</sup> BSB) healing dressing combined with autologous platelet-rich gel (APG) in the treatment of diabetic foot ulcer (DFU). Methods: A total of 120 patients with DFU hospitalized in the Changsha Central Hospital from August 2020 to September 2021 were selected and randomly divided into an experimental group (BSB + APG, n = 60) and a control group (BSB, n = 60) according to random number table method. The total therapeutic effect, healing time, hospital stay, level indexes of various inflammatory factors before and after treatment and ulcer area were observed in the two groups. Results: The total effect of the control group was worse than that of the experimental group, and the data between the two groups were significant (P 0.05);after treatment, the levels of inflammatory factors including WBC, CRP, IL-6 and TNF-α in the control group were higher than those in the experimental group, and there was significant difference between the two groups (P 0.05);after 14 days of treatment, the ulcer area in the control group was larger than that in the experimental group, and the data between the two groups were significant (P Conclusion: BSB combined with APG can achieve better therapeutic effect, reduce the inflammatory reaction of patients, and promote wound healing in the treatment of patients with diabetic foot ulcer.
文摘In this study, with borneol fragments in the crystallized mother liquor of natural borneol used as the raw materials, supercritical carbon dioxide method is adopted for refining to get high purity borneol. The result of the experiment shows that the yield and purity are excellent with an extraction pressure of 11 MPa, an extracting temperature of 40°C, a carbon dioxide flow rate of 25 L·h<sup>-</sup><sup>1</sup> and an extraction time of 20 minutes. After detected by gas chromatography, the purity of the crystallization products could reach 96%.
基金supported by the National Natural Science Foundation of China (Nos. 81173564,81274028 and 81274102)
文摘A gas chromatography mass spectrometry （GC-MS） method has been developed and fully validated for the simultaneous determination of natural borneol （NB） and its metabolite, camphor, in rat plasma. Following a single liquid-liquid extraction, the analytes were separated using an HP-5MS capillary column （0.25 mm ？ 30 m ？ 0.25μm） and analyzed by MS in the selected ion monitoring mode. Selected ion monitor （m/z） of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats.
文摘BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.
文摘Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described. The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced. The application of borneol as a natural ingredient added to functional cosmetics was summarized, and its effects on skin-spot treatment, acne skin care, eczema skin care, skin repair and anti-oxidation were introduced. Finally, the possible problems in the application of borneol in cosmetics were put forward, and the application prospect of borneol in the development of cosmetics was given.
文摘Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described.The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced.The application of borneol as a natural ingredient added to functional cosmetics was summarized,and its effects on skin-spot treatment,acne skin care,eczema skin care,skin repair and anti-oxidation were introduced.Finally,the possible problems in the application of borneol in cosmetics were put forward,and the application prospect of borneol in the development of cosmetics was given。
基金This work was supported by Project of Natural Science Foundation of Shandong province(No.ZR2020MH343).
文摘Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.
基金supported by National Key R&D Program of China(2020YFA0908000)the CACMS Innovation Fund(CI2021A04109,CI2023D002,China)Key project at central government level:the ability to establish sustainable use of valuable Chinese Medicine Resources(2060302,China).
文摘(+)-Borneol,the main component of"Natural Borneol"in the Chinese Pharmacopoeia,is a high-end spice and precious medicine.Plant extraction cannot meet the increasing demand for(+)-borneol,while microbial biosynthesis offers a sustainable supply route.However,its production was extremely low compared with other monoterpenes,even with extensively optimizing the mevalonate pathway.We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate(BPP),which suffers the side-reaction and the competition from the cellular dephosphorylation process,especially lipid metabolism,thus limiting(+)-borneol synthesis.Here,we systematically optimized the dephosphorylation process by identifying,characterizing phosphatases,and balancing cellular dephosphorylation metabolism.For the first time,we identified two endogenous phosphatases and seven heterologous phosphatases,which significantly increased(+)-borneol production by up to 152%.By engineering BPP dephosphorylation and optimizing the MVA pathway,the production of(+)-borneol was increased by 33.8-fold,which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks,so far the highest reported in the literature.This study showed that rewiring dephosphorylation metabolism was essential for high-level production of(+)-borneol in Saccharomyces cerevisiae,and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.
基金supported by 2021 Traditional Chinese Medicine(Medicine of South China)Industry Talents Project-Innovation Team of South China Medicine Resources,Yunfu and the State Administration of Traditional Chinese Medicine high-level key discipline construction project(No.zyyzdxk-2023186)。
文摘As a traditional Chinese medicine(TCM),borneol has shown superior ability for anti-infammatory and analgesic activities when coupled with other active ingredients from ancient times.Furthermore,borneol is believed to improve blood concentration and bioavailability of drugs.Thus,it has been paired with various TCM formulas since ancient time.The physiological barriers in human can cause signifcant limitations in drug effciency as the drug is primarily restricted from entering into blood and brain.Borneol has been proven to enhance the permeability of biological barriers such as the blood–brain,transdermal,corneal,and intestinal barriers.Moreover,growing interest has been shown in the drug delivery system design for trans-barrier transport involving borneol.Nano-drug delivery system with increased surface area and improved active sites,has been applied to increase the bioactivity of water insoluble drugs.Nano-drug delivery system has been used to enhance drug effcacy by reducing the time of action as compared to conventional administration approach of TCM formulas.Given its ability to enhance crossbarrier permeation and drug effcacy,borneol has been integrated into TCM formulas of drug delivery system for precise and prolonged targeting at tumor sites.However,the design and preparation of a drug delivery system consisting of borneol still face great challenges.Current research fails to unravel the difference in mechanism of action between nano-drug delivery systems comprised of borneol and conventional drug systems coupled with borneol.Enhanced penetration of borneol in drug delivery system is rarely verifed compared to conventional administration with identical drug formulation consisting of borneol regarding dosage and medical indications.This study outlines the current state of research on the properties,formulation and pharmacological effects of borneol,allowing cross-comparison of borneol coupled with single compound and classical TCM formulas for various medical indications.This study aims to provide insights into the design of borneol-based enhanced cross-barrier delivery drug formulation,and the potential development of nano-drug system for TCM formulas with borneol for enhanced bioavailability.
