Withanolides from the active extract of Physalis angulate and their anti-hepatic fibrosis effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.

Acupoint application therapy alleviates pain by regulating immune function through inhibiting TLR4/MyD88/NF-κB p65 signaling in a primary dysmenorrhea rat model. / 穴位贴敷通过TLR4/MyD88/NF-κBé€šè·¯è°ƒèŠ‚åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„å ç–«åŠŸèƒ½.

OBJECTIVES: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea. METHODS: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased(P<0.001), and the rats showed writhing reaction (P<0.01). The spleen index and thymus index were significantly decreased(P<0.01, P<0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased(P<0.001, P<0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased(P<0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased (P<0.001). The spleen index and thymus index were significantly increased(P<0.01, P<0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased(P<0.001, P<0.05, P<0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased(P<0.001, P<0.01). CONCLUSIONS: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

Integrated metabolomics and network pharmacology revealed the key active ingredients for the treatment of ulcerative colitis in the Citrus reticulata 'Dahongpao' peel.

Citrus reticulata pericarpium (CRP), the peel of Citrus reticulata 'Dahongpao' (DHP) is a medicinal herb with significant therapeutic value for treating ulcerative colitis (UC). However, the active therapeutic components of CRP are unclear. This study aims to reveal the metabolites potentially associated with the pharmacological properties of CRP. We performed flavonoid-targeting metabolomics to characterize the components of CRP (anti-UC part), tangerine pith and Citrus reticulata semen (no anti-UC effects parts) of DHP and further screened active components of CRP using network pharmacology and molecular docking. Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used to study the anti-inflammatory effect of the selected biologically active components. The therapeutic effects of the selected components were further investigated in a mouse model of UC induced by DSS. Three compounds, namely nobiletin, sinensetin, and hispidulin had the lowest docking scores among all screened ingredients. IL-6 and NO concentrations were significantly decreased in the LPS-stimulated RAW264.7 cells compared with control cells treated with these compounds. Moreover, UC mice treated with these compounds showed a reversal in weight loss, inhibition of shortening of colon length, and amelioration of colon injury. Our results indicated that sinensetin, nobiletin, and hispidulin can be potentially used for the treatment of UC.

Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome-mediated Caspase-1/GSDMD pyroptosis pathway.

Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin-eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis-related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase-1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p-NF-κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis-related proteins NLRP3, Caspase-1, ASC, and GSDMD, reversed the levels of IL-1ß, IL-18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome-mediated Caspase-1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP.

From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.

Comparing Western and traditional Chinese medicine for male sexual dysfunction: can Klotho represent a silk road?

Traditional Chinese medicine (TCM) and Western Medicine both have shown efficacy in treating male sexual dysfunction (MSD). The aim of this perspective paper is to discuss a possible link between Western medicine and TCM in the MSD field as represented by the entity of Klotho. Klotho is a recently discovered protein, mainly expressed in the kidney, encoded by the anti-aging gene klotho. Not only is Klotho significantly correlated with the development and progression of kidney diseases and their complications, but increasing evidence indicates that it is also closely related to MSD. A comprehensive search within PubMed database was performed to retrieve available evidence on Klotho's roles, particularly in kidney and in MSD. Indeed, in the TCM theory, the concept of the "kidney" is entirely different from the Western medicine: it is closely related to metabolism and to the reproductive, nervous, endocrine systems, being more than just a urinary organ. According to the "Kidney storing essence (jing) and governing reproduction" (KSEGR) theory, a cornerstone in TCM, the treatment of MSD mainly consists of restoring the kidney's function. Signs of decreasing kidney essence show a consistent similarity to deficiencies of Klotho, also for what regards the male sexual function. Based on the current evidence, Klotho may represent a potential biological indicator for sexual desire and sexual function and a kind of new scientific Silk Road between TCM and Western medicine for MSD; nevertheless, there is a need to conduct further high-quality research to prove this hypothesis.

Short-term and long-term effectiveness of acupuncture and Tuina on knee osteoarthritis: study protocol for a randomized controlled trial.

Background: The effectiveness of acupuncture and tuina in treating knee osteoarthritis (KOA) is still controversial, which limits their clinical application in practice. This study aims to evaluate the short-term and long-term effectiveness of acupuncture and tuina on KOA. Methods/design: This parallel-group, multicenter randomized clinical trial (RCT) will be conducted at the outpatient clinic of five traditional Chinese medicine hospitals in China. Three hundred and thirty participants with KOA will be randomly assigned to acupuncture, tuina, or home-based exercise group with a ratio of 1:1:1. The primary outcome is the proportion of participants achieving a minimal clinically important improvement defined as a ≥ 12% reduction on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain dimension on short term (week 8) and long term (week 26) compared with baseline. Secondary outcomes are knee joint conditions (pain, function, and stiffness), self-efficacy of arthritis, quality of life, and psychological conditions, which will be evaluated by the WOMAC score and the Patient Global Assessment (PGA), and in addition, the respondents index of OMERACT-OARSI, Short Form 12 Health Survey (SF-12), arthritis self-efficacy scale, and European five-dimensional health scale (EQ-5D). Adverse events will be collected by self-reported questionnaires predefined. Clinical trial registration: https://www.chictr.org.cn.

Efficacy of acupuncture for psychogenic erectile dysfunction: a randomized, sham-controlled trial.

BACKGROUND: Psychogenic erectile dysfunction (pED) is a common sexual dysfunction often accompanied by psychosomatic factors. Its treatment includes oral medications, psychotherapy, and behavioral therapy. Acupuncture's effect on erectile function in pED patients remains to be investigated. This randomized study evaluated the effects of acupuncture and sham acupuncture in pED patients. Altogether, 66 men with pED were randomized to the acupuncture (n = 33) or sham acupuncture group (n = 33). Both groups have a 6-week treatment with 18 sessions. Primary outcome was the International Index of Erectile Function-5 (IIEF-5) at 6 weeks. Secondary outcomes were IIEF-5 (weeks 2, 4, and 10), erection hardness score (EHS), sexual encounter profile-2 (SEP-2), SEP-3, self-rating anxiety scale (SAS), and self-rating depression scale (SDS). RESULTS: Among the 66 participants, 64 completed the outcome measurements at week 10. Both acupuncture and sham acupuncture groups had improved IIEF-5 and EHS and decreased SAS and SDS post-treatment (p < 0.05). The acupuncture group had significantly better improvement in IIEF-5, EHS, and SEP-3 and significantly reduced SAS and SDS than the sham acupuncture group (p < 0.05). The improvement in SEP-2 post-treatment was not significantly different between the two groups (p > 0.05). There were no serious adverse events. CONCLUSIONS: The 6-week acupuncture treatment significantly improved the erectile capacity and psychosomatic status of pED patients. TRIAL REGISTRATION: ChiCTR2200064345 (Chinese Clinical Trial Registry) ( https://www.chictr.org.cn/showproj.html?proj=174873 ).

RéSUMé: CONTEXTE: La dysfonction érectile psychogène (DEp) est une dysfonction sexuelle courante, souvent accompagnée de facteurs psychosomatiques. Son traitement comprend des médicaments par voie orale, une psychothérapie, et une thérapie comportementale. L'effet de l'acupuncture sur la fonction érectile chez les patients atteints de DEp reste à étudier. Cette étude randomisée a évalué les effets de l'acupuncture et de l'acupuncture simulée chez les patients atteints de DEp. Au total, 66 hommes atteints de DEp ont été répartis par randomisation dans le groupe d'acupuncture (n = 33) ou d'acupuncture simulée (n = 33). Les deux groupes ont eu un traitement de 6 semaines avec 18 séances. Le critère de jugement principal était l'indice international de la fonction érectile-5 (IIEF-5) à six semaines. Les critères de jugement secondaires étaient l'IIEF-5 (semaines 2, 4 et 10), le score dedureté de l'érection (EHS), le profil de rencontre sexuelle-2 (SEP-2), le SEP-3, l'échelle d'auto-évaluation de l'anxiété (SAS) et l'échelle d'auto-évaluation de la dépression (SDS). RéSULTATS: Parmi les 66 participants, 64 ont complété les mesures souhaitées à la semaine 10. Les groupes d'acupuncture et d'acupuncture simulée présentaient une amélioration de l'IIEF-5 et de l'EHS et une diminution du SAS et du SDS après le traitement (p < 0,05). Le groupe d'acupuncture a eu une amélioration significativement meilleure de l'IIEF-5, de l'EHS et du SEP-3 et une réduction significative de la SAS et de la SDS par rapport au groupe d'acupuncture simulée (p < 0,05). L'amélioration post-traitement du SEP-2 n'était pas significativement différente entre les deux groupes (p > 0,05). Il n'y a pas eu d'effets indésirables graves. CONCLUSIONS: Le traitement par acupuncture de six semaines a significativement amélioré la capacité érectile et l'état psychosomatique des patients atteints de dysfonction érectile psychogène (DEp). NUMéRO D'ENREGISTREMENT DE L'ESSAI: ChiCTR2200064345 (Registre chinois des essais cliniques) ( https://www.chictr.org.cn/showproj.html?proj=174873 ) Date d'inscription : 3 octobre 2022. MOTS-CLéS: Acupuncture; psychogène; Dysfonction érectile; Acupuncture simulée; Dysfonction sexuelle.

Acupoint compatibility effect: increasing "effect value" and expanding "effect domain". / è §ç©´é ä¼æ•ˆåº”.

By summarizing and exploring the theoretic connotation, key of functions and effect mechanism of acupoint compatibility, the effect of acupoint compatibility is concluded as the increase of "effect value" and the expansion of "effect domain". The increase of "effect value" is the concrete embodiment by the value of medical assessment scale, the value of objective index detection in clinical trial and the value of index detection in experiment research. The expansion of "effect domain" is the increase of effect target and the extension of effect scope. The paper interprets the scientific connotation of acupoint compatibility therapy from a new perspective, and emphasizes the innovative approaches to research while bringing forth new ideas on the research method. It is anticipated that a novel breakthrough can be achieved in the study of acupoint compatibility and the improvement of acupuncture-moxibustion efficacy.

Mechanism of Shugan Yidan fan, a Chinese herbal formula, in rat model of premature ejaculation.

BACKGROUND: Premature ejaculation (PE) is one of the most common forms of sexual dysfunction in men, and multimodal therapeutic regimens should be considered to treat the condition. We developed a Chinese medicine herbal medicine, Shugan Yidan fang that had a significant clinical effect on PE patients, extending the time between penetration and ejaculation. However, the mechanism of this formula remains unclear. There is evidence that PE is associated with peripheral neuropathology, and the actions of dopamine (DA) and 5-hydroxytryptamine (5-HT). The aim of this study was to investigate the mechanism of Shugan Yidan fang's effect on PE through the relationship between sexual behavioristics and the level of neurotransmitters and dopamine receptors (DARs). RESULTS: We showed that the male PE groups had a significant PE phenotype compared to healthy rats. Treatment with Shugan Yidan fang improved the behavioristics of the PE rats, and reduced the expression of DAR mRNA and protein while improving dopamine transporter levels. CONCLUSIONS: Our study provided evidence for the beneficial effect of Shugan Yidan fang in PE therapy, and proposed a preliminary potential mechanism for the clinical application of the formula.

RéSUMé: CONTEXTE: L'éjaculation précoce (EP) est l'une des formes les plus courantes de dysfonction sexuelle chez les hommes, et des régimes thérapeutiques multimodaux doivent être envisagés pour traiter la maladie. Nous avons développé une phytothérapie de médecine chinoise, dénommée Shugan Yidan fang, qui a eu un effet clinique significatif sur les patients atteints d'EP, prolongeant le temps entre la pénétration et l'éjaculation. Le mécanisme d'action de cette formule reste cependant flou. Il existe des preuves que l'EP est associée à une neuropathologie périphérique et aux actions de la dopamine (DA) et de la 5-hydroxytryptamine (5-HT). Le but de cette étude était d'étudier le mécanisme de l'effet de Shugan Yidan sur l'EP à travers la relation entre les comportements sexuels et le niveau de neurotransmetteurs et de récepteurs de la dopamine (DAR). RéSULTATS: Nous avons montré que les groupes PE mâles avaient un phénotype PE significatif par rapport aux rats sains. Le traitement avec Shugan Yidan fang a amélioré les comportements sexuels des rats PE et a réduit l'expression de l'ARNm DAR et des protéines, tout en améliorant les niveaux de de transporteurs de la dopamine. CONCLUSIONS: Notre étude a fourni des preuves de l'effet bénéfique du Shugan Yidan dans la thérapie de la PE, et a proposé un mécanisme potentiel préliminaire pour l'application clinique de la formule.

[Efficacy, safety, and mechanism of Huangkui Capsules in treating chronic kidney disease: Meta-analysis and integrative bioinformatics].

Meta-analysis and integrative bioinformatics were employed to comprehensively study the efficacy, safety, and mechanism of Huangkui Capsules in treating chronic kidney disease(CKD). CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, and Web of Science were searched for randomized controlled trial(RCT) of Huangkui Capsules for CKD from inception to January 3, 2023. The outcome indicators included urine protein, serum creatinine(Scr), and blood urea nitrogen(BUN) levels, and Cochrane Handbook 5.1 and RevMan 5.3 were employed to perform the Meta-analysis of the included RCT. The active ingredients of Huangkui Capsules were retrieved from CNKI, and the targets of CKD from GeneCards, OMIM, and TTD. Cytoscape 3.8.0 was used to build a "component-disease" network and a protein-protein interaction(PPI) network for the screening of core components and targets. Next, a differential analysis of the core targets of Huangkui Capsules for treating CKD was conducted with the clinical samples from GEO to identify the differentially expressed core targets, and correlation analysis and immune cell infiltration analysis were then performed for these targets. A total of 13 RCTs were included for the Meta-analysis, involving 2 372 patients(1 185 in the observation group and 1 187 in the control group). Meta-analysis showed that the Huangkui Capsules group and the losartan potassium group had no significant differences in reducing the urinary protein levels after 12(MD=19.60, 95%CI[-58.66, 97.86], P=0.62) and 24 weeks(MD=-66.00, 95%CI[-264.10, 132.11], P=0.51) of treatment. Huangkui Capsules in combination with conventional treatment was superior to conventional treatment alone(MD=-0.55, 95%CI[-0.86,-0.23], P=0.000 6). Huangkui Capsules combined with conventional treatment was superior to conventional treatment alone in recovering Scr(MD=-9.21, 95%CI[-15.85,-2.58], P=0.006) and BUN(MD=-1.02, 95%CI[-1.83,-0.21], P=0.01). Five patients showed clear adverse reactions, with abdominal or gastrointestinal discomfort. Huangkui Capsules had 43 active ingredients and 393 targets, and the core ingredients were myricetin, quercetin, gossypin, elaidic acid, dihydromyricetin, isochlorogenic acid B, and caffeic acid. CKD and Huangkui Capsules shared 247 common targets, including 25 core targets. The GEO differential analysis predicted 18 differentially expressed core targets, which were mainly positively correlated with immune cell expression and involved in immune inflammation, oxidative stress, pyroptosis, lipid metabolism, sex hormone metabolism, and cell repair. Conclusively, Huangkui Capsules combined with conventional treatment significantly reduced urine protein, Scr, and BUN. Huangkui Capsules alone and losartan potassium had no significant difference in reducing urine protein. This efficacy of Huangkui Capsules may be associated with the multi-component, multi-target, and multi-pathway responses to immune inflammation and oxidative stress. The included RCT had small sample sizes and general quality. More clinical trial protocols with large sample sizes and rigorous design and in line with international norms are needed to improve the evidence quality, and the results of bioinformatics analysis remain to be confirmed by further studies.

Exploring the roles of microorganisms and metabolites in the 30-year aging process of the dried pericarps of Citrus reticulata 'Chachi' based on high-throughput sequencing and comparative metabolomics.

GuangChenpi (GCP), the dried pericarps of Citrus reticulata 'Chachi', has been consumed daily as a food and dietary supplement in China for centuries. Its health benefits are generally recognized to be dependent on storage time. However, the specific roles of microorganisms and metabolites during long-term storage are still unclear. In this study, comparative metabolomics and high-throughput sequencing techniques were used to investigate the effects of co-existing microorganisms on the metabolites in GCP stored from 1 to 30 years. In total, 386 metabolites were identified and characterized. Most compounds were flavonoids (37%), followed by phenolic acids (20%). Seventeen differentially upregulated metabolites were identified as potential key metabolites in GCP, and 8 of them were screened out as key active ingredients by Venn diagram comparative analyses and verified by network pharmacology and molecular docking. In addition, long-term storage could promote the accumulation of secondary metabolites. Regarding the GCP microbiota, Xeromyces dominated the whole 30-year aging process.Moreover, Spearman correlation analysis indicated that Bacillus thuringiensis and Xeromyces bisporus, the dominant bacterial and fungal species, were strongly associated with the key active metabolites. Our results suggested that the change of active ingredients caused by the dominant microbial is one of the mechanisms affecting the GCP aging process. Our study provides novel functional insights and research perspectives on microorganism-associated metabolite changes that may improve the GCP aging process.

Acupuncture for premature ejaculation: a systematic review and meta-analysis.

Background: Although acupuncture is widely used to treat premature ejaculation (PE), its effectiveness remains highly controversial. Aim: To evaluate the efficacy and safety of acupuncture on PE. Methods: According to the relevant keywords, 11 major English and Chinese databases were searched for randomized controlled trials (RCTs) of acupuncture alone or in combination with other treatments for PE. The quality of evidence across studies was assessed by the GRADEpro tool. Outcomes: Study outcome measures included the intravaginal ejaculation latency time (IELT), the Premature Ejaculation Diagnostic Tool (PEDT), the Chinese Index of Premature Ejaculation-5 (CIPE-5), treatment success rate, and adverse events. Results: Seven trials were included in this review for a total of 603 participants. A low quality of evidence suggests that it is not possible to determine whether acupuncture, as compared with a selective serotonin reuptake inhibitor, has an advantage in improving the IELT (standardized mean difference [SMD], -1.75; 95% CI, -6.12 to 2.63; P = .43, I2 = 98%), PEDT scores (SMD, 0.32; 95% CI, -0.68 to 1.32; P = .53, I2 = 85%), and treatment success rate (risk ratio, 0.69; 95% CI, 0.41-1.14; P = .15). However, participants receiving acupuncture had a lower CIPE-5 (SMD, -1.06; 95% CI, -1.68 to -0.44; P < .01). As compared with sham acupuncture, acupuncture significantly improved the IELT (SMD, 1.47; 95% CI, 1.01-1.92; P < .01, I2 = 0%) and PEDT scores (SMD, -1.23; 95% CI, -1.78 to -0.67; P < .01, I2 = 37%). When compared with other treatments alone, a combined treatment with acupuncture can significantly improve the IELT (SMD, 7.06; 95% CI, 2.53-11.59; P < .01, I2 = 97%), CIPE-5 (SMD, 0.84; 95% CI, 0.45-1.22; P < .01, I2 = 0%), and treatment success rate (SMD, 1.60; 95% CI, 1.18-2.16; P < .01, I2 = 53). Clinical Implications: The results suggest a significant effect of acupuncture in the treatment of certain important indicators of PE; however, this finding needs to be treated with caution because of the quality of the RCTs included. Strengths and Limitations: Comprehensive inclusion of available RCTs has been performed. However, limitations include a low number of studies and a lack of detailed information to allow subgroup analysis. Conclusion: The present systematic review and meta-analysis show that acupuncture has a significant effect on several subjective PE parameters, such as improving the feeling of control over ejaculation and distress, particularly when used in an integrated way. However, due to the low quality of evidence, acupuncture still needs larger well-designed RCTs to be confirmed.

Effect of zinc supplementation on blood sugar control in the overweight and obese population: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although overweight and obese people have a higher risk of type 2 diabetes incidence than normal-weight individuals, the efficacy of zinc supplementation in blood sugar control in overweight and obese people remained unknown. This meta-analysis attempted to address this issue. METHODS: Databases including PubMed, Embase, and the Cochrane Library were searched from inception until May 2022 to identify randomized controlled trials (RCTs) investigating the effects of zinc supplementation among participants who were overweight or obese without language restriction. It is a random-effect meta-analysis that analyzed the impact of zinc supplementation on fasting glucose (FG) (i.e., primary outcome) and other variables including fasting insulin (FI), homeostasis model assessment-insulin resistance index (HOMA-IR), glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and 2-hour postprandial glucose (2 h- PG). RESULTS: Analysis of 12 eligible RCTs involving 651 overweight/obese participants demonstrated that zinc supplementation significantly improves FG (weighted mean difference [WMD]: -8.57 mg/dL; 95% confidence interval [CI]: -14.04 to -3.09 mg/dL, p = 0.002), HOMA-IR (WMD: -0.54; 95% CI: -0.78 to -0.30, p < 0.001), HbA1c (WMD: -0.25%; 95% CI: -0.43% to -0.07%, p = 0.006), and 2 h-PG (WMD: -18.42 mg/dL; 95% CI: -25.04 to -11.79 mg/dL, p < 0.001) compared to those in the control group. After conducting subgroup analyses, we found that the primary outcome, FG, showed more significant results in the subgroups with Asia, Zinc supplementation alone, higher dose (≥30 mg) and patients with diabetes. CONCLUSION: Our meta-analysis indicated that zinc supplementation benefits blood sugar control in overweight and obese populations, with an especially significant reduction in FG.

[Assay of amino acids in leaves of Eucommia ulmoides under arbor forest mode and leaf-oriented cultivation mode by pre-column derivatization HPLC].

This study aims to develop the pre-column derivatization high performance liquid chromatography(HPLC) method for the determination of 16 kinds of amino acids in Eucommia ulmoides leaves, and compare the content of amino acids in the leaves harvested at different time and under leaf-oriented cultivation mode(LCM) and arbor forest mode(AFM). The HPLC conditions are as below: phenyl isothiocyanate(PITC) as pre-column derivatization agent, Agilent ZORBAX C_(18 )column(4.6 mm×250 mm, 5 µm), mobile phase A of acetonitrile-water(80∶20), mobile phase B of 0.1 mol·L~(-1) sodium acetate solution-acetonitrile(94∶6), gradient elution, flow rate of 1.0 mL·min~(-1), injection volume of 5 µL, column temperature of 40 ℃, and detection wavelength of 254 nm. The HPLC profile indicated well separation of 16 kinds of amino acids and the amino acid content in E. ulmoides leaves was up to 16.26%. In addition, the amino acid content in leaves of E. ulmoides under LCM was higher than under AFM. The amino acid content varied with the harvesting time. Through orthogonal partial least squares discriminant analysis, the amino acids of E. ulmoides under LCM and AFM were compared, which can distinguish the leaves under LCM from those under AFM. Principal component analysis was applied to comprehensively score the amino acids of E. ulmoides leaves. The results showed that the score of leaves under LCM was higher than that under AFM. Nutritional evaluation results indicated that the proteins in E. ulmoides leaves belonged to high-quality vegetable proteins. The established method for the determination of amino acid content is reliable. With the amino acid content as index, the leaf quality of E. ulmoides under LCM is better than that under AFM. This study lays a theoretical basis for the promotion of LCM for E. ulmoides and the development of medicinal and edible products from E. ulmoides leaves.

[Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition].

To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. The experimental results showed that VFD and DS basically kept the original color of MFOEU. The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. Considering the color of MFOEU, the suitable drying methods were DS and VFD. Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas.

Effects of Danggui-Shaoyao-San on central neuroendocrine and pharmacokinetics in female ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine formula Danggui-Shaoyao-San (DSS) has been reported to have estrogen-like effects and therapeutic effects on the symptoms of Alzheimer's disease (AD). AIM OF THE STUDY: To explore whether the central oxytocin and neuroendocrine system is involved in the modulating effects of DSS on the cognition and neuropsychiatric hebaviors in female AD rats, and to investigate the pharmacokinetics of paeoniflorin and ferulic acid in female AD rats with DSS treatment. MATERIAL AND METHODS: DSS (1.2, 3.2, 8.6 g/kg/day) was orally administered to ovariectomized (OVX) rats, and saline was orally administered to sham operation rats as control group. The Morris water maze test, novel object recognition test, and passive avoidance test were conducted for evaluation of learning and memory abilities, while elevated plus maze test and forced swim test were performed to assess anxiety- and depressive-like behaviors. ELISA kits were used to detect the levels of estrogen (E), estrogen receptor α (ERα), oxytocin (OT), oxytocin receptor (OTR), acetylcholine (Ach), acetylcholin esterase (AchE), and choline acetyl transferase (ChAT) in the cortex. The concentrations of Ach, glutamate (Glu), γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) in the hippocampus were assessed by HPLC-MS. The changes of neuronal morphology in the hippocampus were observed by Nissl staining. The pharmacokinetics of paeoniflorin and ferulic acid in OVX rats with DSS treatment were studied by HPLC. RESULTS: In the Morris water maze test, novel object recognition test, and passive avoidance test, OVX rats showed cognitive impairment. In the elevated plus maze test and forced swim test, the anxiety- and depressive-like behaviors of OVX rats were significant as compared to the control group. Treatment of DSS significantly imporved the cognitive deficits, and ameliorated anxiety- and depressive-like behaviors of OVX rats. The expression of E, ERα, OT, OTR, AchE and ChAT in the cortex of model group were significantly decreased, and DSS significantly reversed these changes. The concentrations of Ach, Glu, GABA, 5-HT and NE in the hippocampus of OVX rats were significantly decreased, whereas DSS significantly increased the levels of Ach, Glu, GABA, 5-HT and NE. There was no significant difference in the concentration of DA in the hippocampus among groups. Degenerating neurons in the hippocampal CA3 region were observed in OVX rats, and the number of neurons was decreased. DSS treatment reduced the degenerating neurons, and incresed the number of neurons. The MRT (0 - ∞), AUC (0 - ∞), Cmax and t1/2z values of paeoniflorin, and the AUC 0-∞ and Cmax value of ferulic acid were higher in DSS-treated OVX rats than those in the DSS-treated control rats. CONCLUSIONS: DSS improves the learning and memory ability, and attenuates anxiety- and depressive-like behaviors of OVX rats. The mechanism may be through increasing estrogen, reducing cholinergic damage, and modulating neurotransmitters. The increase in absorption and elimination time of paeoniflorin and ferulic acid in OVX rats may enhance the efficacy of DSS.

Tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium sibiricum Patrin ex Widder (X. sibiricum) are widely used traditional herbal medicines for arthritis treatment in China. Rheumatoid arthritis (RA) is characterized by progressive destructions of joints, which is accompanied by chronic, progressive inflammatory disorder. According to our previous research, tomentosin was isolated from X. sibiricum and revealed anti-inflammatory activity. However, the potential therapeutic effect of tomentosin on RA and the anti-inflammatory mechanism of tomentosin remain to be clarified. The present study lays theoretical support for X. sibiricum in RA treatment, also provides reference for further development of X. sibiricum in clinic. AIM OF THE STUDY: To investigate the effect of tomentosin in collagen-induced arthritis (CIA) mice and reveal its underlying mechanism. MATERIALS AND METHODS: In vivo, tomentosin (10, 20 and 40 mg/kg) was given to CIA mice for seven consecutive days, to evaluate its therapeutic effect and anti-inflammatory activity. In vitro, THP-1-derived macrophages were used to verify the effect of tomentosin on inflammation. Then, molecular docking and experiments in vitro was conducted to predict and explore the mechanism of tomentosin inhibiting inflammation. RESULTS: Tomentosin attenuated the severity of arthritis in CIA mice, which was evidenced by the swelling of the hind paws, arthritis scores, and pathological changes. Particularly, tomentosin effectively reduced the ratio of M1 macrophage and TNF-α levels in vitro and vivo. Then, molecular docking and experiments in vitro was carried out, indicating that tomentosin inhibited M1 polarization and TNF-α levels accompanied by the increase of MERTK and up-regulated GAS6 levels. Moreover, it has been proved that GAS6 was necessary for MERTK activation and tomentosin could up-regulate GAS6 levels effectively in transwell system. Further mechanistic studies revealed that tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6 in transwell system. CONCLUSION: Tomentosin relieved the severity of CIA mice by inhibiting M1 polarization. Furthermore, tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

Risk assessment of metal(loid)s in tea from seven producing provinces in China.

To evaluate metal(loid) contamination in tea leaves and assess health risks of tea drinking in China, metal(loid) concentrations in tea leaves from major tea-producing provinces were determined. Nine metal(loid)s (Al, Cr, Co, Ni, Cu, Zn, As, Cd and Pb) were measured in a total of 217 tea samples representing five tea varieties (black tea, dark tea, green tea, oolong tea and white tea) from seven major tea-producing provinces of China (Fujian, Guangdong, Henan, Hunan, Jiangsu, Yunnan and Zhejiang). The results indicated that tea samples from Hunan Province had the highest metal(loid) concentrations, likely due its high prevalence of heavy industrial activities and soil pollution. The concentrations of As and Pb in dark tea were markedly higher than those in other tea varieties. A strong Spearman correlation coefficient (0.78, P < 0.001) of As and Pb in all the tea varieties has also been found, indicating their similar sources. Human health risk assessment for the nine analyzed metal(loid)s indicated that co-exposure to these metal(loids) may not cause significant health risks (hazard index [HI] > 1 suggests considerable health risks). Among the five tea varieties, metal(loids)s in dark and green tea induced relatively higher health risks, with 90th percentile HI values approached 0.8. Co (53.6 %-84.5 %) and Al (3.33 %-15.8 %) made the highest contributions to the HI of the selected tea commodities. Thus, public and regulatory agencies should reduce excessive Co and Al accumulation in these tea varieties during cultivation and production processes.