AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its...AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration(3 × 10^(-7) mol/L to 1 × 10^(-4)mol/L). We then determined the responses of the proximal and distal colon segments of rats to the folowing stimuli:(1) carbachol(1 × 10^(-9) mol/L to 1 × 10^(-5) mol/L);(2) neurotransmitter antagonists including N~ω-nitro-l-arginine methyl ester hydrochloride(10μmol/L) and(1 R~*, 2 S~*)-4-[2-Iodo-6-(methylamino)-9 Hpurin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt(1 μmol/L);(3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt(100 μmol/L); and(4) single KCl doses(120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA(100 μmol/L) for 1 min. Electrical-field stimulation(40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined.RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration(EC_(50)) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response(mg contractions) in the PA + KCl-treated IBS-D group(11.87 ± 3.34) was significantly decreased in the peak tension(P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle(EC_(50) = 0.94 μmol/L) was significantly decreased by PA(EC_(50) = 37.43 μmol/L)(P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced(10 μmol/L) contraction(P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stressinduced IBS-D rats.CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.展开更多
Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chine...Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chinese herb patchouli,was developed into biomimetic liposomes for macrophagetargeting delivery for IBD treatment.The developed lactoferrin-modified liposomes(LF-lipo)can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy.LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-κB pathway.LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1βactivation.LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model,evidenced by the reduced disease activity index,the improved colon functions,and the downregulated inflammatory cytokines in the colon.LF-lipo provided an effective and safe macrophagetargeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management.展开更多
Objective:To investigate the antibacterial activity of patchouli alcohol(PA)against 127 bacteria strains,including the common bacteria and drug-resistant bacteria strains both in the in vitro and in vivo tests.Methods...Objective:To investigate the antibacterial activity of patchouli alcohol(PA)against 127 bacteria strains,including the common bacteria and drug-resistant bacteria strains both in the in vitro and in vivo tests.Methods:For the in vitro trial,the antibacterial property of PA against 107 Gram-positive and 20 Gram-negative bacteria strains was screened by agar double dilution method.For the in vivo trial,specific pathogen free Kunming strain of both male and female white mice,were used to test the protective ability of PA after being injected with the median lethal dose of the tested strains.Results:PA possessed antibacterial activity against all the tested 127 strains.In the in vitro test,PA could inhibit both Gram-negative bacteria(25-768μg/m L)and Gram-positive bacteria(1.5-200μg/m L).Particularly,PA was active against some drug-resistant bacteria like methicillin-resistant Staphylococcus aureus(MRSA).PA also exhibited in vivo anti-MRSA activity in mice via intraperitoneal injection.PA could protect mice entirely infected with MRSA at 100 and 200 mg/kg,while 80% mice injected with MRSA could be protected at a low dose of 50 mg/kg.Conclusion:PA might be a potential antibacterial drug from natural sources and might be worthy to explore its mechanism and application in further study.展开更多
Objective: To explore the anti-nociceptive effect of patchouli alcohol(PA), the essential oil isolated from Pogostemon cablin(Blanco) Bent, and determine the mechanism in molecular levels. Methods: The acetic acid-ind...Objective: To explore the anti-nociceptive effect of patchouli alcohol(PA), the essential oil isolated from Pogostemon cablin(Blanco) Bent, and determine the mechanism in molecular levels. Methods: The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to con?rm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor(MOR). Cyclooxygenase 2(COX2)and MOR of mouse brain were expressed for determination of PA’s target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. Results: PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution(P<0.01) and allodynia after intra-plantar formalin(P<0.01) in mice. PA also up-regulated COX2 mRNA and protein(P<0.05) with a down-regulation of MOR(P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level(P<0.05) induced by PA may play an important role in its anti-nociceptive effect.PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Conclusions: Both COX2 and MOR are involved in the mechanism of PA’s anti-nociceptive effect,and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA’s effect on MOR.展开更多
Enantiomerically pure 6-acetyl-1,3,3-trimethyl bicyclo[2.2.2]octan-2-one,a key inter- mediate for synthesis of(-)-patchouli alcohol,was facilely synthesized from the adduct of a monome- thylated(-)-carvone 2 and methy...Enantiomerically pure 6-acetyl-1,3,3-trimethyl bicyclo[2.2.2]octan-2-one,a key inter- mediate for synthesis of(-)-patchouli alcohol,was facilely synthesized from the adduct of a monome- thylated(-)-carvone 2 and methyl acrylate.展开更多
基金Supported by the National Natural Science Foundation of China,No.81573715Natural Science Foundation of Guangdong Province,China,No.2015A030313348Science and Technology Program of Guangzhou,China,No.201510010257
文摘AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration(3 × 10^(-7) mol/L to 1 × 10^(-4)mol/L). We then determined the responses of the proximal and distal colon segments of rats to the folowing stimuli:(1) carbachol(1 × 10^(-9) mol/L to 1 × 10^(-5) mol/L);(2) neurotransmitter antagonists including N~ω-nitro-l-arginine methyl ester hydrochloride(10μmol/L) and(1 R~*, 2 S~*)-4-[2-Iodo-6-(methylamino)-9 Hpurin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt(1 μmol/L);(3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt(100 μmol/L); and(4) single KCl doses(120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA(100 μmol/L) for 1 min. Electrical-field stimulation(40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined.RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration(EC_(50)) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response(mg contractions) in the PA + KCl-treated IBS-D group(11.87 ± 3.34) was significantly decreased in the peak tension(P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle(EC_(50) = 0.94 μmol/L) was significantly decreased by PA(EC_(50) = 37.43 μmol/L)(P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced(10 μmol/L) contraction(P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stressinduced IBS-D rats.CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.
基金the financial support of National Natural Science Foundation of China(Nos.81925035,81673382 and 81521005)the Strategic Priority Research Program of Chinese Academy of Sciences(XDA12050307,China)+2 种基金National Special Project for Significant New Drugs Development(2018ZX09711002-010-002,China)Shanghai Sci Tech Innovation Initiative(19431903100 and 18430740800,China)the Fudan-SIMM Joint Research Fund(FU-SIMM20174009,China)for the support
文摘Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chinese herb patchouli,was developed into biomimetic liposomes for macrophagetargeting delivery for IBD treatment.The developed lactoferrin-modified liposomes(LF-lipo)can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy.LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-κB pathway.LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1βactivation.LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model,evidenced by the reduced disease activity index,the improved colon functions,and the downregulated inflammatory cytokines in the colon.LF-lipo provided an effective and safe macrophagetargeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management.
基金Supported by the National Key Technology Research and Development Program of China(No.2009BAI84B00)。
文摘Objective:To investigate the antibacterial activity of patchouli alcohol(PA)against 127 bacteria strains,including the common bacteria and drug-resistant bacteria strains both in the in vitro and in vivo tests.Methods:For the in vitro trial,the antibacterial property of PA against 107 Gram-positive and 20 Gram-negative bacteria strains was screened by agar double dilution method.For the in vivo trial,specific pathogen free Kunming strain of both male and female white mice,were used to test the protective ability of PA after being injected with the median lethal dose of the tested strains.Results:PA possessed antibacterial activity against all the tested 127 strains.In the in vitro test,PA could inhibit both Gram-negative bacteria(25-768μg/m L)and Gram-positive bacteria(1.5-200μg/m L).Particularly,PA was active against some drug-resistant bacteria like methicillin-resistant Staphylococcus aureus(MRSA).PA also exhibited in vivo anti-MRSA activity in mice via intraperitoneal injection.PA could protect mice entirely infected with MRSA at 100 and 200 mg/kg,while 80% mice injected with MRSA could be protected at a low dose of 50 mg/kg.Conclusion:PA might be a potential antibacterial drug from natural sources and might be worthy to explore its mechanism and application in further study.
基金Supported by the National Natural Science Foundation of China(No.81374006 and No.81073092)the Special Foundation for New Drug Innovation of Tsinghua University(No.20142000077),China
文摘Objective: To explore the anti-nociceptive effect of patchouli alcohol(PA), the essential oil isolated from Pogostemon cablin(Blanco) Bent, and determine the mechanism in molecular levels. Methods: The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to con?rm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor(MOR). Cyclooxygenase 2(COX2)and MOR of mouse brain were expressed for determination of PA’s target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. Results: PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution(P<0.01) and allodynia after intra-plantar formalin(P<0.01) in mice. PA also up-regulated COX2 mRNA and protein(P<0.05) with a down-regulation of MOR(P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level(P<0.05) induced by PA may play an important role in its anti-nociceptive effect.PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Conclusions: Both COX2 and MOR are involved in the mechanism of PA’s anti-nociceptive effect,and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA’s effect on MOR.
基金This project was supported by the National Natural Science Foundation of China.
文摘Enantiomerically pure 6-acetyl-1,3,3-trimethyl bicyclo[2.2.2]octan-2-one,a key inter- mediate for synthesis of(-)-patchouli alcohol,was facilely synthesized from the adduct of a monome- thylated(-)-carvone 2 and methyl acrylate.
