The role of Chinese herbal medicine in the treatment of diabetic nephropathy by regulating endoplasmic reticulum stress.

Diabetic nephropathy (DN), a prevalent microvascular complication of diabetes mellitus, is the primary contributor to end-stage renal disease in developed countries. Existing clinical interventions for DN encompass lifestyle modifications, blood glucose regulation, blood pressure reduction, lipid management, and avoidance of nephrotoxic medications. Despite these measures, a significant number of patients progress to end-stage renal disease, underscoring the need for additional therapeutic strategies. The endoplasmic reticulum (ER) stress response, a cellular defense mechanism in eukaryotic cells, has been implicated in DN pathogenesis. Moderate ER stress can enhance cell survival, whereas severe or prolonged ER stress may trigger apoptosis. As such, the role of ER stress in DN presents a potential avenue for therapeutic modulation. Chinese herbal medicine, a staple in Chinese healthcare, has emerged as a promising intervention for DN. Existing research suggests that some herbal remedies may confer renoprotective benefits through the modulation of ER stress. This review explores the involvement of ER stress in the pathogenesis of DN and the advancements in Chinese herbal medicine for ER stress regulation, aiming to inspire new clinical strategies for the prevention and management of DN.

Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. It has become a leading cause of death in patients with diabetes and end-stage renal disease. Ferroptosis is a newly discovered pattern of programmed cell death. Its main manifestation is the excessive accumulation of intracellular iron ion-dependent lipid peroxides. Recent studies have shown that ferroptosis is an important driving factor in the onset and development of DN. Ferroptosis is closely associated with renal intrinsic cell (including renal tubular epithelial cells, podocytes, and mesangial cells) damage in diabetes. Chinese herbal medicine is widely used in the treatment of DN, with a long history and definite curative effect. Accumulating evidence suggests that Chinese herbal medicine can modulate ferroptosis in renal intrinsic cells and show great potential for improving DN. In this review, we outline the key regulators and pathways of ferroptosis in DN and summarize the herbs, mainly monomers and extracts, that target the inhibition of ferroptosis.

Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2.

Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (Mpro) of SARS-CoV-2 as an example. We first used molecular docking to identify molecular components of the formula which may inhibit Mpro. Baicalein (HQA004) is the most favorable inhibitory ligand. We also identified a ligand from the other component, cubebin (CHA008), which may act to support the proposed HQA004 inhibitor. Molecular dynamics simulations were then performed to further elucidate the possible mechanism of inhibition by HQA004 and synergistic bioactivity conferred by CHA008. HQA004 bound strongly at the active site and that CHA008 enhanced the contacts between HQA004 and Mpro. However, CHA008 also dynamically interacted at multiple sites, and continued to enhance the stability of HQA004 despite diffusion to a distant site. We proposed that HQA004 acted as a possible inhibitor, and CHA008 served to enhance its effects via allosteric effects at two sites. Additionally, our novel wavelet analysis showed that as a result of CHA008 binding, the dynamics and structure of Mpro were observed to have more subtle changes, demonstrating that the inter-residue contacts within Mpro were disrupted by the synergistic ligand. This work highlighted the molecular mechanism of synergistic effects between different herbs as a result of allosteric crosstalk between two ligands at a protein target, as well as revealed that using the multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis to discover novel combination drugs from a Chinese herbal remedy is an innovative pathway.

Effects and safety of Chinese herbal medicine on inflammatory biomarkers in cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials.

Inflammation drives cardiovascular disease (CVD) in individuals with underlying chronic inflammatory diseases, including People with HIV (PWH), independently of dyslipidemia. Adjunctive treatments that lower inflammation may be useful to lower CVD risk in such populations. There is very little data on the efficacy of Chinese herbal medicine (CHM) in reducing inflammation in PWH to address its potential in reducing this CVD risk factor, therefore we evaluated its impact on inflammatory biomarkers relevant to CVD risk in the general population. Six English and Chinese databases were searched for studies investigating CHM's effects on inflammatory biomarkers relevant to CVD from respective inceptions to February 2022. A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted and the most-frequently prescribed herbs were identified. Thirty-eight RCTs involving 4,047 participants were included. Greater than or equal to 50% of included studies had a low risk of bias in five domains (random sequence generation, detection, attrition, reporting and other bias) and 97% had a high risk of performance bias. CHM provided significant additive effects on attenuating relevant inflammatory indices including hs-CRP (SMD -2.05, 95% CI -2.55 to -1.54), IL-6 (SMD -1.14, 95% CI -1.63 to -0.66) and TNF-α levels (SMD -0.88, 95% CI -1.35 to -0.41), but no significant effects on hs-CRP were found between CHM and placebo when co-treating with Western drugs (MD 0.04, 95% CI -1.66 to 1.74). No severe adverse events were reported in CHM groups. The two most prevalent herbs present in formulae demonstrating reduction of at least one inflammatory biomarker were Dan shen (Salviae Miltiorrhizae Radix et Rhizoma) and Huang qi (Astragali Radix). CHM, in combination with standard anti-inflammatory medications, may depress inflammation and reduce the risk of inflammatory conditions such as CVD. Rigorously-conducted trials and adequate reporting are needed to provide more robust evidence supporting the use of CHM to reduce CVD risk in people with underlying chronic inflammation such as PWH.

The clinical evaluation of electroacupuncture combined with mindfulness meditation for overweight and obesity: study protocol for a randomized sham-controlled clinical trial.

BACKGROUND: Overweight and obesity have reached an epidemic level which impacts individual health and creates a financial burden worldwide. Evidence has shown that electroacupuncture is effective for weight loss when combined with lifestyle intervention, while mindfulness meditation can enhance the outcome of weight loss programs. This study aims to evaluate the safety and the add-on effect of electroacupuncture and mindfulness meditation for weight management in overweight and obesity. METHODS/DESIGN: This is a sham-controlled, three-armed randomized clinical trial. A total of 165 participants with BMI between 25 and 39.99 and aged between 18 and 60 who meet the inclusion and exclusion criteria will be randomized into [1] electroacupuncture plus mindfulness meditation group, [2] sham electroacupuncture plus mindfulness meditation group, and [3] electroacupuncture only group. The total duration of this study will be 22 weeks, which consists of a 2-week run-in period, a 12-week intervention period, and an 8-week follow-up period. Participants will receive 12 weekly treatments during the intervention period. Primary outcomes will include body mass index, waist and hip ratio, and body composition. Secondary outcomes will be measured by the Weight-Related Symptom Measure, Obesity and Weight Loss Quality of Life, the Power of Food Scale, and the Chinese medicine differential diagnosis questionnaire. Outcomes will be assessed at the baseline, and endpoints of the 3rd, 6th, 9th, 12th, 14th, 16th, and 20th week. DISCUSSION: This clinical trial will investigate the add-on effect of two combined interventions for weight loss treatment. The findings of this study may contribute to the development of a cost-effective and multidisciplinary weight management approach. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000964213. Registered on 07 June 2018.

The Effects and Safety of Chinese Herbal Medicine on Blood Lipid Profiles in Placebo-Controlled Weight-Loss Trials: A Systematic Review and Meta-Analysis.

This study was conducted to assess the effects and safety of Chinese herbal medicine (CHM) on blood lipids among adults with overweight or obesity. Fourteen bibliographic databases were comprehensively searched, from their respective inceptions up to April 2021, for randomised placebo-controlled weight-loss trials using CHM formulation on total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol over ≥4 weeks. Data collection, risk of bias assessment, and statistical analyses were guided by the Cochrane Handbook (v6.1). Continuous outcomes were expressed as the mean difference with 95% confidence intervals, and categorical outcomes were expressed as a risk ratio with 95% confidence intervals. All analyses were two-tailed with a statistical significance of p < 0.05. Fifteen eligible studies with 1,533 participants were included in this meta-analysis. Findings from meta-analyses indicated that CHM interventions, compared to placebo, reduced triglyceride (MD -0.21 mmol/L, 95% CI -0.41 to -0.02, I 2 = 81%) and increased HDL cholesterol (MD 0.16 mmol/L, 95% CI 0.04 to 0.27, I 2 = 94%) over a median of 12 weeks. The reduction in total cholesterol and LDL cholesterol were not statistically significant. Furthermore, the tendency of reduced triglycerides was identified among overweight participants with high baseline triglycerides. Attrition rates and frequency of adverse events were indifferent between the two groups. CHM may provide lipid-modulating benefits on triglycerides and HDL cholesterol among participants with overweight/obesity, with the tendency for significant triglyceride reduction observed among overweight participants with high baseline triglycerides. However, rigorously conducted randomised controlled trials with larger sample sizes are required to validate these findings.

Feasibility of self-administered acupressure for allergic rhinitis: a pilot randomized controlled trial and lessons learnt for future studies.

OBJECTIVES: Allergic rhinitis (AR) is an immunoglobulin (Ig)E-mediated inflammatory condition that is highly prevalent worldwide. The aim of this pilot trial was to evaluate the feasibility and safety of self-administered acupressure for AR. METHODS: A randomized, single-blind, non-specific controlled clinical trial was conducted at Royal Melbourne Institute of Technology (RMIT) University, Melbourne, Australia. Fifteen AR patients were randomized into two groups: self-administered acupressure at five specific acupressure (SA) points or five non-specific acupressure (NSA) points (1 min/point, twice a day), and treated for 4 weeks with an 8-week follow-up period. The primary outcome was the change in 7-point scale symptom severity. Secondary outcomes included the rhinoconjunctivitis quality of life questionnaire and standardized activities (RQLQs), medication usage, adverse events and participants' opinions of the blinding method. The Statistical Package for the Social Science (SPSS) version 26 was used for data analyses. RESULTS: Fourteen participants completed the study and no major adverse events were reported. No statistically significant differences between SA and NSA groups were identified in 7-point scale symptom severity scores, RQLQs or medication usage. However, participants in the SA group believed that SA was useful for AR and recommended it for self-care. The credibility of the blinding method was successful. No adverse effects were considered to be related to the intervention. CONCLUSION: Acupressure is feasible and appears to be safe for self-administration by AR sufferers. Experience from this pilot study has guided minor amendments to the protocol. A large-scale randomized controlled trial is warranted to further investigate the efficacy and safety of self-administered acupressure for the management of AR.

Chinese Herbal Medicine for Weight Management: A Systematic Review and Meta-Analyses of Randomised Controlled Trials.

Objective: This review investigated the effects and safety of Chinese herbal medicine (CHM) formulas on weight management. Methods: Eighteen databases in English, Chinese, Korean, and Japanese were searched from their inceptions to September 2019. The treatment groups included CHM formulations, and the control included placebo, Western medication (WM), and lifestyle intervention (LI), with or without cointerventions (WM and/or LI). Quality of studies was assessed using Cochrane Collaboration's risk of bias assessment tool. Body weight and body mass index (BMI) were analysed in RevMan v5.4.1 and expressed as mean differences with 95% confidence intervals (CI), while adverse events were expressed as risk ratio with 95% CI. Results: Thirty-nine RCTs were eligible for qualitative analysis, 34 of which were included in the meta-analyses. The majority of studies had a high or unclear risk of selection, performance, and detection bias. Twenty-five CHM studies involving cointerventions revealed that CHM had significant adjunct effects on body weight and BMI at the end of treatment compared to control. No serious adverse events were reported in the CHM groups. Conclusion: CHM indicates a promising adjunct to facilitate WM or lifestyle change for weight management. However, methodological barriers such as lack of allocation concealment and double-blinding may have led to challenges in data synthesis. More rigorously designed RCTs involving cointerventions are warranted.

Phytochemistry, pharmacodynamics, and pharmacokinetics of a classic Chinese herbal formula Danggui Beimu Kushen Wan: A review.

Danggui Beimu Kushen Wan (DBKW) is a classic herbal formula for difficult urination and has been widely used for urinary-related disorders and cancers in current clinical practice. This study aimed to comprehensively review the phytochemistry, pharmacodynamics, and pharmacokinetics of DBKW in experimental studies. We searched 21 databases to identify experimental studies of DBKW. We also searched 11 databases to identify and summarize compounds from DBKW's ingredients. A total of 423 studies of DBKW were identified and 15 studies were included. For Angelicae Sinensis Radix (ASR) and Sophorae Flavescentis Radix (SFR), 2,425 and 2,843 studies were identified, and 42 and 33 studies were included, respectively. Eight compounds were found in the whole formula, 408 compounds from ASR, and 277 compounds from SFR. DBKW may have anticancer effects (inhibiting the growth of tumors, regulating cell proliferation, inducing tumor cell apoptosis, suppressing invasion and metastasis of cancer, enhancing the therapeutic effects of chemotherapy, and relieving toxicity of chemotherapy) and have benefits on chronic prostatitis (reducing inflammation, inhibiting oxidation, regulating sex hormone, and stimulating immune system). The pharmacokinetics of the seven primary compounds from DBKW were also summarized. DBKW contains multiple compounds that may act on more than one pathway of the conditions simultaneously.

Oral application of Chinese herbal medicine for allergic rhinitis: A systematic review and meta-analysis of randomized controlled trials.

Chinese herbal medicine (CHM) has long been used for allergic rhinitis (AR). This systematic review aimed to investigate the clinical effects and safety of oral CHM for AR by comparing it to Western medications (WM). Nineteen databases were searched up to May 27, 2020. Randomized controlled trials (RCTs) assessing the effects of CHM on the primary or secondary outcomes comparing to WM, in any age of the patients, were included. The pooled results were expressed as mean difference, standardized mean difference, or odds ratio with 95% confidence intervals. Eighteen RCTs were included and 17 of them were evaluated in the meta-analysis. CHM may improve total nasal symptom scores, individual symptom scores (rhinorrhea, nasal congestion, sneezing, and nasal itching), quality of life, and recurrence rate, compared to antihistamines (loratadine and chlorpheniramine). Only mild and transient adverse events of CHM were reported. However, there were no significant differences in some subgroup analyses in total nasal symptom scores, rhinorrhea, nasal obstruction, sneezing, nasal itching, and SF-36. Due to the small number of included studies, poor quality of trial design, and substantial heterogeneities, the potential of CHM for AR should be validated in large, multicenter, and well-designed RCTs in the future.

Inhibitory effect of a weight-loss Chinese herbal formula RCM-107 on pancreatic α-amylase activity: Enzymatic and in silico approaches.

Reducing carbohydrates digestion by having a low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107 (Slimming Plus), an eight-herb formula that is modified from RCM-104, indicated significant weight-loss action in clinical trials. However, no published research has studied its mechanism of action on reducing carbohydrate absorption via suppressing the activities of porcine pancreatic alpha-amylase (PPA). In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact. Therefore, our data has provided new knowledge on the mechanisms of action of the RCM-107 formula and its individual herbal ingredients for weight loss, in terms of decreasing carbohydrate digestion via the inhibition of pancreatic alpha-amylase.

Traditional medicines for asthma in children and adults: A systematic review of placebo-controlled studies.

BACKGROUND: Traditional medicines (TMs) adjunctive to conventional medications are widely used for asthma in east-Asia and have gained popularity in western countries. OBJECTIVE: To assess the efficacy and safety of TMs for asthma in children and adults based on placebo-controlled trials in order to inform physicians and assist them in discussions with patients. METHODS: Seventeen electronic databases were searched. Participants had acute or chronic asthma. Interventions included orally administered traditional medicines used in east-Asia. Outcomes included lung function, symptoms, quality of life, exacerbations, medication use and safety. RevMan 5.3 (random effect model) was used for meta-analysis. Baseline values were assessed for balance and asthma severity. Within-group changes were calculated to assess minimal clinically important difference (MCID). RESULTS: Eighteen studies (2080 participants) were included. All combined TMs with conventional medicines. The single study of acute asthma (n = 300) showed an improvement. For chronic asthma, severity at baseline ranged from very mild to severe. When asthma was mild, significant differences in lung function (FEV1%, PEF/R) were not detectable. When participants had moderate and/or severe asthma at baseline improvements were more evident. For measures of lung function, improvements within the TM groups tended to be greater when the asthma was more severe. Some studies showed MCIDs. No serious adverse events or interactions were reported but safety data were incomplete. CONCLUSIONS: The application of certain traditional herbal medicines used in east-Asia as adjuncts to conventional medications improved outcomes in acute and chronic asthma, but most evidence was based on single trials. Therefore, no single TM could be recommended. Effect sizes varied according to asthma severity at baseline. Future studies should consider baseline severity when enrolling participants.

The inhibitory effects of an eight-herb formula (RCM-107) on pancreatic lipase: enzymatic, HPTLC profiling and in silico approaches.

AIMS: Obesity is a global, public health issue that causes or exacerbates serious medical disorders. Chinese herbal therapies have become one of the most popular alternatives due to intolerances of current anti-obesity treatments. The RCM-107 formula (granule) is modified from our previous studied RCM-104 formula, which has demonstrated significant effects on weight reduction in randomized clinical trials. Up to date, there is no published scientific evidence to evaluate the effect of this formula on the weight-loss target pancreatic lipase and therefore, the aim of this study is to investigate the inhibitory effect of RCM-107 and respective individual ingredient on the pancreatic lipase activities. MAIN METHODS: Fluorometric based enzymatic assays, high-performance thin-layer chromatography (HPTLC) profiling and in silico molecular docking techniques were used to investigate the lipase inhibitory effects of the RCM-107 herbal formula and its respective individual herbs. PRINCIPLE FINDINGS: The results demonstrated the potent lipase suppressing effect of the RCM-107 formula. The majority of the ingredients from this formula also showed pancreatic lipase inhibitory activities. The presence of the known weight-loss compounds such as (-)-epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), (-)-epicatechin (EC), rutin, crocin and caffeine were identified in the RCM-107 and related single herbs using HPTLC profiling approaches. In addition, EGCG, EC and the known lipase antagonist orlistat acted on the same site. These compounds form hydrogen bonds with corresponding residues HIS152, ASP80 and GLY77, which can be considered as markers of important areas in the ligand-binding site. This may explain the details of their roles in inhibiting pancreatic lipase activities. CONCLUSION: Our data has provided new knowledge to the mechanistic properties of the RCM-107 formula and its respective individual herbal ingredients for weight loss, in terms of reducing lipid absorption via the inhibition of pancreatic lipase.

Chinese herbal formulae for the treatment of menopausal hot flushes: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to evaluate the therapeutic effects and safety of Chinese herbal medicine (CHM) formulae for managing menopausal hot flushes (MHF). METHODS: Seven English and Chinese databases were searched for studies from respective inceptions to February 2019. Randomized controlled trials investigating the clinical effects and safety of CHM formulae on MHF were considered for inclusion. The outcomes of subjective feelings (MHF and quality of life), objective changes (hormones and peripheral blood flow) and safety were analyzed. The most frequently prescribed formulae and herbs were summarized. RESULTS: Nineteen randomized clinical trials involving 2469 patients were included. When compared to menopausal hormone therapy, CHM had similar effects to menopausal hormone therapy on total effectiveness rate (OR 1.41, 95% CI 0.84 to 2.35) and total Kupperman index (KI) score (SMD -0.13, 95% CI -0.61 to 0.36), and could significantly reduce vasomotor symptom score (MD -0.43, 95% CI -0.55 to -0.31) and upper-body peripheral blood flow (MD -3.56, 95% CI -5.14 to -1.98 under the jaw, MD -7.10, 95% CI -11.01 to -3.19 in the fingertip). When compared to placebo, CHM could reduce MHF severity (MD -0.70, 95% CI-1.00 to -0.40) and improve total KI score (MD -12.61, 95% CI -15.21 to -10.01). However, no statistically significant changes to hormone levels were detected. Most commonly seen adverse events were mild gastrointestinal tract reactions. The most popularly studied formula was Kun Tai capsule and the most frequently prescribed herb was Bai shao (Paeoniae Radix Alba, Paeonia lactiflora Pall.). More than 50% included studies had low risks of bias in the domains of selection, performance, attrition and reporting. CONCLUSIONS: This review indicated that CHM formulae were safe to be applied in MHF females and able to improve MHF-related symptom scores as well as the peripheral blood flow. Further studies should focus on specific formulae.

Guizhi Fuling Wan for uterine fibroids: A systematic review of in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The therapeutic effects of Guizhi Fuling Wan (GFW) on uterine fibroids have been tested on various animal models, but to date, the findings of these studies have not been comprehensively synthesised. This study aimed to evaluate the preclinical effects of GFW on uterine fibroids in different animal models. MATERIALS AND METHODS: Twenty databases were searched from their earliest recorded publications to March 2019 to identify in vivo studies of non-modified GFW compared with no treatment for animal models with uterine fibroids. The methodological quality was assessed using the ARRIVE guidelines. Two groups of outcome measures were evaluated: fibroid characteristics (uterine weight, coefficient or smooth muscle thickness) and sex hormones indexes (oestradiol, progesterone or the gene expression of their receptors). RESULTS: A total of 21 studies (22 experiments) involving 461 female animals met the eligibility criteria. The quality of the included studies scored at 14.24 ±â€¯1.00 out of 20. Four animal species were used and induced by oestrogen or oestrogen combined with progesterone, including guinea pig (n = 20), rats (n = 385, SD and Wister) and mice (n = 56). Overall, the available evidence suggests that GFW has potentially beneficial effects over placebo on both fibroid characteristics and sex hormones in SD rats (except progesterone), Wister rats (except progesterone receptor [PR] gene expression) and ICR mice (except PR gene expression). GFW appears to reduce uterine weight and smooth muscle thickness in the guinea pig, but no data on sex hormone index was available. CONCLUSION: Noting the unevenly distributed covariates of animal model types, experimental evidence suggested that GFW may be a promising intervention for the management of uterine fibroids in animal models. Future natural product studies should be optimised by reporting the voucher specimen. More studies on composition and providing evidence of the involvement of relevant cell signalling pathways are required.

A Classic Herbal Formula Guizhi Fuling Wan for Menopausal Hot Flushes: From Experimental Findings to Clinical Applications.

A classic herbal formula Guizhi Fuling Wan (GFW) has been used for managing menopausal hot flushes (MHFs), but the evidence across different study types has not been systematically summarized. This project investigated the clinical effects, phytochemistry, pharmacodynamics, and potential mechanisms of actions of GFW on the causative target proteins potentially driving MHFs. Twenty English and Chinese databases were searched for relevant clinical and experimental studies. A total of 12,988 studies were identified, of which 46 were included. Seven clinical studies demonstrated GFW had no statistically significant changes in the frequency and severity of MHFs; however, it could improve peripheral blood flow in the fingertips, jaw, and toes. Thirty-five studies on phytochemistry identified 169 chemical compounds of GFW. Four experimental studies revealed GFW's therapeutic effects (e.g., normalize calcitonin gene-related peptide [CGRP] level) and potential target protein/cytokine (estrogen receptor beta [ESR2] with genetic variation, CGRP receptor, and interleukin-8) on MHFs. Therapeutic effects across different study types were inconsistent, possibly due to the dose difference and genotype variety of ESR2 in the human population. Further clinical and experimental studies, as well as biochemical investigation on the mechanisms of actions of GFW, are recommended.

Fritillariae Thunbergii Bulbus: Traditional Uses, Phytochemistry, Pharmacodynamics, Pharmacokinetics and Toxicity.

Fritillariae Thunbergii Bulbus (FTB) has been widely used as an antitussive herb for thousands of years in China. However, FTB's traditional uses, chemical compounds and pharmacological activities have not been systematically reviewed. This study aimed to review its traditional uses, phytochemistry, pharmacodynamics, pharmacokinetics and toxicity. We searched the Encyclopedia of Traditional Chinese Medicine to explore the historical records which indicate that it acts to clear heat, resolve phlegm, relieve cough, remove toxicity and disperse abscesses and nodules. We searched 11 databases to identify potential phytochemical or pharmacological studies. Characteristics of its chemical constituents, pharmacological effects, pharmacokinetic and toxicity were descriptively summarized. A total of 9706 studies were identified and 83 of them were included. As a result, 134 chemical constituents were identified, including 26 alkaloids, 29 compounds found in essential oils, 13 diterpenoids, two carbohydrates, two sterols, 18 amino acids, six nucleosides, four nucleobases, four fatty acids, three lignans, and 27 elements. Thirteen pharmacological effects of FTB were identified, including anti-cancer, tracheobronchial relaxation, antitussive, expectorant, anti-muscarinic, anti-inflammation, anti-thyroid, regulation of blood rheology, antiulcer, anti-diarrhea, pain suppression, antioxidation and neuroprotection. These pharmacological activities may be mainly attributed to the alkaloids in FTB. Further phytochemical, pharmacological and network pharmacological studies are recommended.

Tang-Tong-Fang Confers Protection against Experimental Diabetic Peripheral Neuropathy by Reducing Inflammation.

Tang-tong-fang (TTF) is a Chinese herbal formula that has been shown to be beneficial in diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying mechanism of protection in nerve ischemia provided by TTF is still unclear. We hypothesized that TTF alleviates DPN via inhibition of ICAM-1 expression. Therefore, we tested the effect of TTF in a previously established DPN model, in which nerve injury was induced by ischemia/reperfusion in streptozotocin-induced diabetic rats. We found that the conduction velocity and amplitude of action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by TTF treatment. In addition, TTF treatment also attenuated the effect of DPN on other parameters including histology and ultrastructural changes, expression of ICAM-1, MPO, and TNF-α in rat sciatic nerves, and plasma sICAM-1 and MPO levels. Together, our data suggest that TTF treatment may alleviate DPN via ICAM-1 inhibition.

The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: a meta-analysis.

CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage kidney disease in developed countries. Current therapy can slow the rate of progression of DN, but eventually end-stage renal failure will occur in a proportion of patients. Identification of new strategies and additional complementary and alternative therapies for treating DN are important. OBJECTIVE: The research team wanted to assess the beneficial and harmful effects of using puerarin plus angiotensin converting enzyme inhibitor (ACEI) compared with using only ACEI for treatment of individuals with stage III DN. DESIGN: The research team performed a meta-analysis of randomized, controlled trials (RCTs) by searching the following electronic databases: (1) the Cochrane Database of Systematic Reviews, (2) the Cochrane Central Register of Controlled Trials (CENTRAL), (3) PubMed, (4) EMBASE (Elsevier), (5) the Allied and Complementary Medicine Database (AMED), (6) the Chinese Biomedicine Database (CBM), (7) the China National Knowledge Infrastructure (CNKI), and (8) the Chinese Biomedical Journals (VIP), with no language restrictions, as well as databases of clinical trials. OUTCOME MEASURES: Measured outcomes included (1) urinary protein measured as urinary albumin excretion rate (UAER) (µg/min) and 24-h urine protein (24-h UP) (mg/24 h); (2) renal function measured as blood urea nitrogen (BUN) (mmol/L) and serum creatinine (SCr) (µmol/L); (3) α1-microglobulin (α1-MG) (mg/24 h) and endothelin-1 (ET-1) (ng/24 h); (4) end points (EPs); and (5) adverse events (AEs). RESULTS: Ten RCTs involving 669 participants were included. All trials were conducted and published in China. Treatment of DN with puerarin plus ACEI significantly decreased the UAER-P < .0001, MD = -23.43 (95% CI, -33.95 to -12.91), and had no effect on 24-h UP-P = .09, MD = -56.76 (95% CI, -122.65 to 9.12); BUN-P = .17, MD = -0.51 (95% CI, -1.24 to 0.21); and SCr-P = .26, MD = -4.43 (95% CI, -12.05 to 3.20). One trial reported abdominal discomfort and nausea (2 cases) in the treatment group. CONCLUSIONS: Puerarin may be a beneficial therapy for treating DN; however, this hypothesis needs to be proven by additional high-quality studies using large samples and multicenter evidence.