Objective To evaluate the therapeutic potential and underlying mechanism of Latakaranja vati(LV)in dehydroepiandrosterone(DHEA)-induced polycystic ovarian syndrome(PCOS)in female Wistar rats through integrated network...Objective To evaluate the therapeutic potential and underlying mechanism of Latakaranja vati(LV)in dehydroepiandrosterone(DHEA)-induced polycystic ovarian syndrome(PCOS)in female Wistar rats through integrated network pharmacology,molecular docking,and experimental validation.Methods Bioactive constituents in LV tablets were identified using liquid chromatographymass spectrometry(LC-MS).Network pharmacology analysis was performed to predict LVrelated targets and PCOS-associated genes using BindingDB,Super-PRED,GeneCards,and DisGeNET databases.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to clarify biological processes and signaling pathways.Molecular docking simulations evaluated binding affinities between LV phytoconstituents and key predicted targets.For in vivo validation,PCOS was induced in 36 female Wistar rats by daily subcutaneous administration of DHEA(60 mg/kg)for 21 d,and after successful model establishment,rats were randomly divided into DHEA,metformin(MET),clomiphene citrate(CC),and LV low-dose(LV-L,51.5 mg/kg),medium-dose(LV-M,103 mg/kg),and high-dose(LV-H,206 mg/kg)groups(n=6 each),which were orally administered for 21 d,respectively.Additional 6 rats were kept as normal control(NC)group,which did not receive any DHEA treatment.Estrous cyclicity,body weight,ovarian weight and diameter,fasting blood glucose(FBG),serum hormones[testosterone,progesterone,estrogen,follicle-stimulating hormone(FSH),luteinizing hormone(LH),and anti-Müllerian hormone(AMH)],insulin resistance[homeostatic model assessment for insulin resistance(HOMAIR)],lipid profile[total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL),and low-density lipoprotein(LDL)],inflammatory cytokines[tumor necrosis factor(TNF)-αand interleukin(IL)-6],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GPx),malondialdehyde(MDA),and nitric oxide(NO)],myeloperoxidase(MPO),and ovarian histopathology were evaluated.Results LC-MS analysis identified eight major phytoconstituents in LV:sitosterol,citrulline,bonducellin,oleic acid,δ-caesalpin,heptocosane,palmitic acid,and stearic acid.Network pharmacology revealed 36 overlapping targets between LV and PCOS,with key targets including estrogen receptor 1(ESR1),nuclear receptor subfamily 3 group C member 1(NR3C1),signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR).GO and KEGG enrichment analyses indicated involvement in lipid metabolism regulation,steroid hormone receptor activity,prolactin signaling pathway,hypoxia-inducible factor(HIF)-1 signaling pathway,and insulin resistance pathways.Molecular docking demonstrated strong binding affinities between LV phytoconstituents and predicted targets,with sitosterol showing the strongest binding to EGFR(−9.9 kcal/mol)and ESR1(−8.3 kcal/mol).In vivo experiments confirmed that LV treatment restored normal estrous cyclicity and significantly reduced body weight,ovarian weight,and ovarian diameter compared with DHEA group(P<0.05,P<0.01,or P<0.001).LV dose-dependently restored FBG,insulin,and HOMA-IR levels(P<0.01 or P<0.001),and improved lipid profile,including reduced TC,TG,and LDL,and increased HDL(P<0.05,P<0.01,or P<0.001).Hormonal abnormalities were corrected with testosterone,LH,and AMH decreased and progesterone,estrogen,and FSH increased(P<0.05,P<0.01,or P<0.001).Furthermore,LV enhanced activities of antioxidant enzymes(SOD,CAT,and GPx),and reduced oxidative stress markers(MDA and NO)(P<0.05,P<0.01,or P<0.001).Pro-inflammatory cytokines TNF-αand IL-6 were significantly suppressed,and MPO activity decreased compared with DHEA group(P<0.05,P<0.01,or P<0.001).Histopathological examination showed that after LV treatment,ovarian morphology recovered with cystic follicles decreased and corpus luteum increased.Among the three LV-treated groups,LV-H group exhibited the most pronounced improvements across all parameters,indicating a clear dose-dependent therapeutic effects.Conclusion LV showed protective effects against DHEA-induced pcos by restoring endocrine balance and mitigating metabolic,oxidative,and inflammatory disturbances.The involvement of key regulatory targets,including ESR1,NR3C1,STAT3,and EGFR,supports its multi-target therapeutic potential.These findings highlight LV as a promising herbal candidate for polycystic ovarian syndrome management.展开更多
An appropriate BRICS institution is expected to be set up to drive cooperation on promoting digitalization,industrialization,inno vati on,in elusive ness,and inv estme nt in BRICS countries.
Venerable(Joborje)Atisa(阿底峡,982-1054),the most prominent figure in the restoration of Buddhism in Xizang after the persecution of the Dharma initiated by King Glaindarma(朗达玛),was a native of Zahor(社护罗国),a re...Venerable(Joborje)Atisa(阿底峡,982-1054),the most prominent figure in the restoration of Buddhism in Xizang after the persecution of the Dharma initiated by King Glaindarma(朗达玛),was a native of Zahor(社护罗国),a region east of Vajrāsana(金刚座),in present-day Bangladesh.His father was King Kalyānasrī(善祥),and his mother,Srīprabhāvati(吉祥光).The king had three sons,namely,Padmagarbha(莲花藏),Candragarbha(月藏)and Srīgarbha(吉藏).The eldest succeeded the royal throne.The second,who afterward assumed the Buddhist name of Dīpamkarasrīj?āna(吉祥燃灯智,Tibetan:Dpalldan marmemdzad yeses)since he received the entire precepts of an ordained monk,was known as Venerable Atisa."Atisa"is an appellation of honor,to which various but mostly implausible explanations were given by later commentators.According to Tsonkhapa(宗喀巴),and The Bkahgdams choshbyun(History of the Bkahgdams Sect,迦当教法史),as quoted in The Lamrim brdabkrol(Glossary of the Great Treatise on the Stages of the Bodhi-Path,菩提道次第广论字诂),"Atisa"means"phulbyun"in Tibetan,a term implying the idea of"transcendent"or"excellent",whereas it may be assumed as a probable derivation from the Sanskrit"Atisaya(殊胜,meaning excellent or transcendent)".展开更多
文摘Objective To evaluate the therapeutic potential and underlying mechanism of Latakaranja vati(LV)in dehydroepiandrosterone(DHEA)-induced polycystic ovarian syndrome(PCOS)in female Wistar rats through integrated network pharmacology,molecular docking,and experimental validation.Methods Bioactive constituents in LV tablets were identified using liquid chromatographymass spectrometry(LC-MS).Network pharmacology analysis was performed to predict LVrelated targets and PCOS-associated genes using BindingDB,Super-PRED,GeneCards,and DisGeNET databases.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to clarify biological processes and signaling pathways.Molecular docking simulations evaluated binding affinities between LV phytoconstituents and key predicted targets.For in vivo validation,PCOS was induced in 36 female Wistar rats by daily subcutaneous administration of DHEA(60 mg/kg)for 21 d,and after successful model establishment,rats were randomly divided into DHEA,metformin(MET),clomiphene citrate(CC),and LV low-dose(LV-L,51.5 mg/kg),medium-dose(LV-M,103 mg/kg),and high-dose(LV-H,206 mg/kg)groups(n=6 each),which were orally administered for 21 d,respectively.Additional 6 rats were kept as normal control(NC)group,which did not receive any DHEA treatment.Estrous cyclicity,body weight,ovarian weight and diameter,fasting blood glucose(FBG),serum hormones[testosterone,progesterone,estrogen,follicle-stimulating hormone(FSH),luteinizing hormone(LH),and anti-Müllerian hormone(AMH)],insulin resistance[homeostatic model assessment for insulin resistance(HOMAIR)],lipid profile[total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL),and low-density lipoprotein(LDL)],inflammatory cytokines[tumor necrosis factor(TNF)-αand interleukin(IL)-6],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GPx),malondialdehyde(MDA),and nitric oxide(NO)],myeloperoxidase(MPO),and ovarian histopathology were evaluated.Results LC-MS analysis identified eight major phytoconstituents in LV:sitosterol,citrulline,bonducellin,oleic acid,δ-caesalpin,heptocosane,palmitic acid,and stearic acid.Network pharmacology revealed 36 overlapping targets between LV and PCOS,with key targets including estrogen receptor 1(ESR1),nuclear receptor subfamily 3 group C member 1(NR3C1),signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR).GO and KEGG enrichment analyses indicated involvement in lipid metabolism regulation,steroid hormone receptor activity,prolactin signaling pathway,hypoxia-inducible factor(HIF)-1 signaling pathway,and insulin resistance pathways.Molecular docking demonstrated strong binding affinities between LV phytoconstituents and predicted targets,with sitosterol showing the strongest binding to EGFR(−9.9 kcal/mol)and ESR1(−8.3 kcal/mol).In vivo experiments confirmed that LV treatment restored normal estrous cyclicity and significantly reduced body weight,ovarian weight,and ovarian diameter compared with DHEA group(P<0.05,P<0.01,or P<0.001).LV dose-dependently restored FBG,insulin,and HOMA-IR levels(P<0.01 or P<0.001),and improved lipid profile,including reduced TC,TG,and LDL,and increased HDL(P<0.05,P<0.01,or P<0.001).Hormonal abnormalities were corrected with testosterone,LH,and AMH decreased and progesterone,estrogen,and FSH increased(P<0.05,P<0.01,or P<0.001).Furthermore,LV enhanced activities of antioxidant enzymes(SOD,CAT,and GPx),and reduced oxidative stress markers(MDA and NO)(P<0.05,P<0.01,or P<0.001).Pro-inflammatory cytokines TNF-αand IL-6 were significantly suppressed,and MPO activity decreased compared with DHEA group(P<0.05,P<0.01,or P<0.001).Histopathological examination showed that after LV treatment,ovarian morphology recovered with cystic follicles decreased and corpus luteum increased.Among the three LV-treated groups,LV-H group exhibited the most pronounced improvements across all parameters,indicating a clear dose-dependent therapeutic effects.Conclusion LV showed protective effects against DHEA-induced pcos by restoring endocrine balance and mitigating metabolic,oxidative,and inflammatory disturbances.The involvement of key regulatory targets,including ESR1,NR3C1,STAT3,and EGFR,supports its multi-target therapeutic potential.These findings highlight LV as a promising herbal candidate for polycystic ovarian syndrome management.
文摘An appropriate BRICS institution is expected to be set up to drive cooperation on promoting digitalization,industrialization,inno vati on,in elusive ness,and inv estme nt in BRICS countries.
文摘Venerable(Joborje)Atisa(阿底峡,982-1054),the most prominent figure in the restoration of Buddhism in Xizang after the persecution of the Dharma initiated by King Glaindarma(朗达玛),was a native of Zahor(社护罗国),a region east of Vajrāsana(金刚座),in present-day Bangladesh.His father was King Kalyānasrī(善祥),and his mother,Srīprabhāvati(吉祥光).The king had three sons,namely,Padmagarbha(莲花藏),Candragarbha(月藏)and Srīgarbha(吉藏).The eldest succeeded the royal throne.The second,who afterward assumed the Buddhist name of Dīpamkarasrīj?āna(吉祥燃灯智,Tibetan:Dpalldan marmemdzad yeses)since he received the entire precepts of an ordained monk,was known as Venerable Atisa."Atisa"is an appellation of honor,to which various but mostly implausible explanations were given by later commentators.According to Tsonkhapa(宗喀巴),and The Bkahgdams choshbyun(History of the Bkahgdams Sect,迦当教法史),as quoted in The Lamrim brdabkrol(Glossary of the Great Treatise on the Stages of the Bodhi-Path,菩提道次第广论字诂),"Atisa"means"phulbyun"in Tibetan,a term implying the idea of"transcendent"or"excellent",whereas it may be assumed as a probable derivation from the Sanskrit"Atisaya(殊胜,meaning excellent or transcendent)".
