Role of herbal medicine and gut microbiota in the prevention and treatment of obesity.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a common metabolic dysfunction disease, which is highly correlated with the homeostasis of gut microbiota (GM). The dysregulation of GM on energy metabolism, immune response, insulin resistance and endogenous metabolites (e.g., short chain fatty acids and secondary bile acids) can affect the occurrence and development of obesity. Herbal medicine (HM) has particular advantages and definite therapeutic effects in the prevention and treatment of obesity, but its underlying mechanism is not fully clear. AIM OF THE STUDY: In this review, the representative basic and clinical anti-obesity studies associated with the homeostasis of GM regulated by HM including active components, single herb and herbal formulae were summarized and discussed. We aim to provide a state of art reference for the mechanism research of HM in treating obesity and the further development of new anti-obesity drugs. MATERIALS AND METHODS: The relevant information was collected by searching keywords (obesity, herbal medicine, prescriptions, mechanism, GM, short chain fatty acids, etc.) from scientific databases (CNKI, PubMed, SpringerLink, Web of Science, SciFinder, etc.). RESULTS: GM dysbiosis did occur in obese patients and mice, whiles the intervention of GM could ameliorate the condition of obesity. HM (e.g., berberine, Ephedra sinica, Rehjnannia glutinosa, and Buzhong Yiqi prescription) has been proved to possess a certain regulation on GM and an explicit effect on obesity, but the exact mechanism of HM in improving obesity by regulating GM remains superficial. CONCLUSION: GM is involved in HM against obesity, and GM can be a novel therapeutic target for treating obesity.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice.

OBJECTIVE: To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice. METHODS: Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing. RESULTS: Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism. CONCLUSION: APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review.

Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.

Network Pharmacology-Based Dissection of the Active Ingredients and Protective Mechanism of the Salvia Miltiorrhiza and Panax Notoginseng Herb Pair against Insulin Resistance.

The Salvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely utilized in traditional Chinese medicine for the longevity and for preventing and treating cardio-cerebrovascular diseases. Often associated with cardio-cerebrovascular diseases are comorbidities such as insulin resistance. However, the protective mechanisms of DQ against insulin resistance remain not well understood. Through network pharmacology analysis, a total of 94 candidate active compounds selected from DQ (61 from S. miltiorrhiza Bunge and 33 from P. notoginseng (Burk.) F. H. Chen) interacted with 52 corresponding insulin resistance-related targets, which mainly involved insulin resistance and the AMPK signaling pathway. Furthermore, the contribution index calculation results indicated 25 compounds as the principal components of this herb pair against insulin resistance. Among them, ginsenoside F2, protocatechuic acid, and salvianolic acid B were selected and validated to promote glucose consumption through activating AMPK phosphorylation and upregulating GLUT4 in insulin-resistant cell model (HepG2/IR) cells. These findings indicated that DQ has the potential for repositioning in the treatment of insulin resistance mainly through the AMPK signaling pathway.

Potential Role of Gut Microbiota in Traditional Chinese Medicine against COVID-19.

The coronavirus disease 2019 (COVID-19) spreads and rages around the world and threatens human life. It is disappointing that there are no specific drugs until now. The combination of traditional Chinese medicine (TCM) and western medication seems to be the current more effective treatment strategy for COVID-19 patients in China. In this review, we mainly discussed the relationship between COVID-19 and gut microbiota (GM), as well as the possible impact of TCM combined with western medication on GM in the treatment of COVID-19 patients, aiming to provide references for the possible role of GM in TCM against COVID-19. The available data suggest that GM dysbiosis did occur in COVID-19 patients, and the intervention of GM could ameliorate the clinical condition of COVID-19 patients. In addition, TCMs (e.g., Jinhua Qinggan granule, Lianhua Qingwen capsule, Qingfei Paidu decoction, Shufeng Jiedu capsule, Qingjin Jianghuo decoction, Toujie Quwen granules, and MaxingShigan) have been proven to be safe and effective for the treatment of COVID-19 in Chinese clinic. Among them, Ephedra sinica, Glycyrrhiza uralensis, Bupleurum chinense, Lonicera japonica,Scutellaria baicalensi, and Astragalus membranaceus are common herbs and have a certain regulation on GM, immunity, and angiotensin converting enzyme 2 (ACE2). Notably, Qingfei Paidu decoction and MaxingShigan have been demonstrated to modulate GM. Finally, the hypothesis of GM-mediated TCM treatment of COVID-19 is proposed, and more clinical trials and basic experiments need to be initiated to confirm this hypothesis.

Cascaded Amplifier Nanoreactor for Efficient Photodynamic Therapy.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on self-assembled nanofusiforms for persistent oxygenation to amplify ROS levels. The nanofusiform assembly is capable of photothermal and photodynamic treatment and regulation of redox oxidation stress by antioxidant depletion to prevent ROS tolerance. The Pt nanozyme decoration of the nanofusiform enables efficient oxygen supplements via Pt nanozyme-catalyzed decomposition of H2O2 overexpressed in TME and generation of O2. Furthermore, the temperature elevation resulted from the photothermal effect of the nanofusiform increases the catalase-like catalytic activity of the Pt nanozyme for boosted oxygen generation. Thus, such a triple cascade strategy using nanozyme-based nanofusiforms amplifies the ROS level by continuous oxygenation, enhancing the efficacy of PDT in vitro and in vivo. Meanwhile, an in vivo multi-modal imaging including near-infrared fluorescence imaging, photothermal imaging, and magnetic resonance imaging achieves precise tumor diagnosis. The rationally designed nanofusiform acts as an efficient ROS amplifier through multidimension strengthening of continuous oxygenation, providing a potential smart nanodrug for cancer therapy.

[Research progress on processing history evolution as well as effect on chemical compositions and traditional pharmacological effects of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma(RRR) is a commonly used traditional Chinese medicine, with extensive pharmacological effects and clinical applications. This paper summarized processing history evolution of RRR and its effect on chemical compositions and pharmacological effects, and provided feasible insights for further studies on the chemical compositions and pharmacological effects of RRR before and after processing. Relevant information demonstrated that RRR has a long history of processing and various methods. At pre-sent, Chinese Pharmacopoeia mainly records four processing methods: cleaning(raw RRR), wine processing(RRR stir-fried with wine), steaming processing(RRR wine steaming), fried charcoal(RRR charring). RRR has a good effect in clearing heat effect, hemostatic effect and blood promoting effect, and its main chemical components are anthraquinone/anthrones, stilbene, phenylbutanone, chromogens, flavonoids and tannin compounds. This paper reviewed the history evolution of RRR and its effect on chemical composition and pharmacological changes, and put forward further study ideas, with the aim to provide a basic reference for processing mechanism, effective material basis and clinical application of RRR.

Quantitative evaluation of Danqi tablet by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry integrated with bioassay.

Danqi tablet composed of the dried roots of Salvia miltiorrhiza and Panax notoginseng is a well-known Chinese patent medicine commonly used for the treatment of cardio-cerebrovascular diseases such as coronary heart disease and myocardial ischemia. Numerous chemical constituents belonging to S. miltiorrhiza and P. notoginseng were detectable in Danqi tablet. Here, we established and validated a rapid and sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry method for simultaneous quantification of 23 components in Danqi tablet and then successfully applied to assay 12 batches of samples from ten manufacturers. Our results demonstrated that the contents of 23 components in 12 batches of Danqi tablets varied significantly and their quality indeed existed differently based on the principal component analysis. According to the quantitative data and the loading plot of principal component analysis, five abundant compounds in Danqi tablet were selected as characteristic chemical markers possibly responsible for the quality assessment. Among them, salvianolic acid B and ginsenoside Rg1 were further chosen to be combined at 2:5 ratio to evaluate the anti-thrombotic activity on phenylhydrazine-induced zebrafish heart thrombosis model. Expectedly, this component combination increased the heart red blood cells intensity compared with the model group and the median effective concentration was 123.4 µg/mL, suggestive of its well anti-thrombotic effect. This study contributed to the quantitative evaluation of Danqi tablet and indicated the combination of salvianolic acid B and ginsenoside Rg1 may be capable of reflecting the effect of Danqi tablet, thereby providing a reference for further investigations on the improvement of quality control and clinical application of Danqi tablet.

Network topology and machine learning analyses reveal microstructural white matter changes underlying Chinese medicine Dengzhan Shengmai treatment on patients with vascular cognitive impairment.

With the increasing incidence of cerebrovascular diseases and dementia, considerable efforts have been made to develop effective treatments on vascular cognitive impairment (VCI), among which accumulating practice-based evidence has shown great potential of the traditional Chinese medicine (TCM). Current randomized double-blind controlled trial has been designed to evaluate the 6-month treatment effects of Dengzhan Shengmai (DZSM) capsules, one TCM herbal preparations on VCI, and to explore the underlying neural mechanisms with graph theory-based analysis and machine learning method based on diffusion tensor imaging (DTI) data. A total of 82 VCI patients were recruited and randomly assigned to drug (45 with DZSM) and placebo (37 with placebo) groups, and neuropsychological and neuroimaging data were acquired at baseline and after 6-month treatment. After treatment, compared to the placebo group, the drug groups showed significantly improved performance in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) score (p < 0.001) and the other cognitive domains. And with the reconstruction of white matter structural network, there were more streamlines connecting the left thalamus and right hippocampus in the drug groups (p < 0.001 uncorrected), with decreasing nodal efficiency of the right olfactory associated with slower decline in the general cognition (r = -0.364, p = 0.048). Moreover, support vector machine classification analyses revealed significant white matter network alterations after treatment in the drug groups (accuracy of baseline vs. 6-month later, 68.18 %). Taking together, the present study showed significant efficacy of DZSM treatment on VCI, which might result from white matter microstructure alterations and the topological changes in brain structural network.

Regulation of serum lipidomics and amino acid profiles of rats with acute myocardial ischemia by Salvia miltiorrhiza and Panax notoginseng herb pair.

BACKGROUND: Salvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely used in traditional Chinese medicine for a long history to prevent and treat the coronary heart disease. However, its protective mechanisms against myocardial ischemia during coronary heart disease remain not well-understood. PURPOSE: In this study, we aimed to explore the protective mechanisms of DQ on myocardial ischemia from the perspective of serum lipidomics and amino acids (AAs). METHODS: Rats were orally administrated with low-dose DQ (L-DQ, 0.24 g/kg) and high-dose DQ (H-DQ, 0.96 g/kg) for two weeks and subcutaneously injected with isoproterenol (ISO, 65 mg/kg) for two consecutive days (13th and 14th days) to induce acute myocardial ischemia (AMI). Heart histopathology and serum biochemical indices were examined. The specifically altered serum lipid metabolites were profiled via lipidomics approach, while serum AA profiles were analyzed using UHPLC-TQ-MS/MS. RESULTS: Cardiac marker enzymes (CK, CK-MB, LDH and cTn-I) were significantly upregulated in AMI rats with some of which significantly dropped to normal level in L- and H-DQ groups. Serum TC, TG, HDL, LDL, VLDL and FFA were improved in AMI rats treatment with L- and H-DQ. Further, the PCA based on lipidomics showed serum lipid metabolites in L- and H-DQ groups were closer to control group than that in model group. Compared with model group, H-DQ pretreatment significantly reduced SM (d34:1) and CE (20:4), and increased FA (20:5), PC (26:1), TG (56:9), TG (54:7), MG (17:0), Cer (d32:0) and Cer (d34:0), whereas L-DQ significantly alleviated the perturbed levels of CE (20:4), FA (20:5), MG (17:0), and SM (d34:1). Moreover, there was a significant increment for leucine, isoleucine, valine, phenylalanine, lysine and glutamate but a significant reduction for tryptophan in the serum of rats in model group as compared to control group. Intriguingly, H-DQ could significantly decrease the levels of glutamate, lysine, isoleucine, and BCAAs (the sum of leucine, isoleucine and valine) after AMI, while L-DQ had no significant effects on the above altered AAs. The Western blotting results implied that H-DQ could promote the myocardial BCAA catabolism in AMI rats by activation of BCKDHA, whereas by inhibition of BCKDHK. CONCLUSION: This study presents evidence for the therapeutic effects of DQ on AMI injury, in part, via co-regulating lipid and AA metabolisms.

Gut microbiota modulation with traditional Chinese medicine: A system biology-driven approach.

With the development of system biology, traditional Chinese medicine (TCM) is drawing more and more attention nowadays. However, there are still many enigmas behind this ancient medical system because of the arcane theory and complex mechanism of actions. In recent decades, advancements in genome sequencing technologies, bioinformatics and culturomics have led to the groundbreaking characterization of the gut microbiota, a 'forgotten organ', and its role in host health and disease. Notably, gut microbiota has been emerging as a new avenue to understanding TCM. In this review, we will focus on the structure, composition, functionality and metabolites of gut microbiota affected by TCM so as to conversely understand its theory and mechanisms. We will also discuss the potential areas of gut microbiota for exploring Chinese material medica waste, Chinese marine material medica, add-on therapy and personalized precise medication of TCM. The review will conclude with future perspectives and challenges of gut microbiota in TCM intervention.

Berberine treatment-emergent mild diarrhea associated with gut microbiota dysbiosis.

Berberine (BBR) is a non-prescription drug to treat various bacteria-associated diarrheas. However, BBR has also been reported to cause diarrhea in clinic, with underlying mechanisms poorly understood. Because altered gut microbial ecology is a potential basis for diarrhea, this study was conducted to investigate the impact of BBR on gut microbiota of treatment-emergent diarrhea. BBR treatment (200 mg/kg, i.g.) in normal rats exhibited no significant changes in serum biochemical parameters but mild diarrhea occurred, accompanied with the decreased gastrointestinal transit time and increased fecal moisture, suggestive of the local effects of BBR in the intestine. Colon histology revealed the decreased abundance of mucus-filled goblet cells in BBR group. Although BBR-treated rats had the enlarged cecum with watery caecal digesta, short-chain fatty acids concentration was significantly lower than control group. Additionally, BBR caused gut microbiota dysbiosis by evaluating the decreased observed species number and Shannon index. BBR increased the relative abundances of families Porphyromonadaceae and Prevotellaceae as well as genera Parabacteroides, Prevotellaceae_UCG-001 and Prevotellaceae_NK3B31_group. Spearman's correlation analysis revealed family Prevotellaceae and genus Prevotellaceae_UCG-001 as the most prominent drivers of the BBR treatment-emergent diarrhea, correlating positively with fecal moisture but negatively with gastrointestinal transit time. This study therefore demonstrated that the treatment-emergent mild diarrhea of BBR was most likely due to the dysbiosis of the gut microbiota.

Cinobufotalin as an effective adjuvant therapy for advanced gastric cancer: a meta-analysis of randomized controlled trials.

Purpose: This study aimed to investigate the efficacy and safety of combining cinobufotalin and chemotherapy for advanced gastric cancer (GC). Patients and methods: Literature retrieval was performed in Cochrane Library, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biological Medicine Database (CBM), Wanfang database and Chinese Scientific Journal Database (VIP) before September 2018. The primary reported outcomes including therapeutic efficacy, quality of life (QoL), and adverse events were systematically evaluated. Results: Data from 27 trials including 1,939 advanced GC patients were included. The results indicated that, compared with chemotherapy alone, the combination of chemotherapy and cinobufotalin significantly improved patients' overall response rate (odds ratio [OR] =1.88, 95% confidence interval [CI] =1.54-2.31, P<0.00001) and disease control rate (OR =2.05, 95% CI =1.63-2.58, P<0.00001). The QoL of patients also evidently improved after chemotherapy and cinobufotalin combined treatment, as indicated by increased QoL improved rate (OR =2.39, 95% CI =1.81-3.15, P<0.00001), Karnofsky Performance Score (OR =7.00, 95% CI =2.25-11.75, P=0.004) and pain relief rate (OR =7.00, 95% CI =2.25-11.75, P=0.004). Adverse events including nausea and vomiting, diarrhea, leukopenia, hand-foot syndrome, anemia, gastrointestinal side effects and peripheral neurotoxicity caused by chemotherapy were evidently alleviated (P<0.05) when cinobufotalin was administered to GC patients. Conclusion: Evidence from the meta-analysis suggested that the combination of chemotherapy and cinobufotalin is more effective in treating GC than chemotherapy alone. It alleviates the adverse effects associated with chemotherapy and improves the QoL of GC patients.

Plasmonic and Photothermal Immunoassay via Enzyme-Triggered Crystal Growth on Gold Nanostars.

Immunoassay is commonly used for the detection of disease biomarkers, but advanced instruments and professional operating are often needed with current techniques. The facile readout strategy for immunoassay is mainly limited to the gold nanoparticles-based colorimetric detection. Here, we show that photothermal nanoparticles can be applied for biosensing and immunoassay with temperature as readout. We develop a plasmonic and photothermal immunoassay that allows straightforward readout by color and temperature based on crystal growth, without advanced equipment. It is demonstrated that alkaline phosphatase-triggered silver deposition on the surface of gold nanostars causes a large blue shift in the localized surface plasmon resonance of the nanosensor, accompanied by photothermal conversion efficiency changes. This approach also allows dual-readout of immunoassays with high sensitivity and great accuracy for the detection of prostate-specific antigen in complex samples. Our strategy provides a promising way for point-of-care testing and may broaden the applicability of programmable nanomaterials for diagnostics.

[Filtration of active fractions with function of expelling water retention with drastic purgative from Kansui Radix stir-baked with vinegar].

To study the function of expelling water retention with drastic purgative of different polarities of Kansui Radix stir-baked with vinegar on the cancerous ascites model rats, the furosemide was taken as positive control drug, and the cancerous ascites model rats were respectively orally administered with different polarities of Kansui Radix stir-baked with vinegar for 7 d. The amount of urine and ascites, the level of urinary sodium, potassium, chloride ion and pH, and the content of PRL1, AII, ALD in serum were investigated. Compared with model groups, ethyl acetate extract group showed a decreasing trend in ascites; the amount of urine of showed a significant increase (P < 0.05); the level of urinary sodium, potassium, chloride ion (P < 0.05, P < 0.01), pH (P < 0.05), and the content of PRL1, AII, ALD in serum all showed a significant decrease (P < 0.01). The effects of petroleum ether extract and n-butanol extract were weaker than that of ethyl acetate extract. The water exact was the weakest. The results showed that ethyl acetate extract is the active part of Kansui Radix stir-baked with vinegar on the function of expelling water retention with drastic purgative on the cancerous ascites model rats, alleviating the water-electrolyte disorder and body fluid acid-base imbalance, regulating the renin angiotensin aldosterone system.

[Study on toxicity of vinegar-processed Kansui Radix on basis of symptom-based prescription theory].

OBJECTIVE: To study the differences in the toxicity of vinegar-processed Kansui Radix on normal and cancerous ascites model rats. METHOD: Normal and cancerous ascites model rats were taken as the research objects and orally administered with different doses of vinegar-processed Kansui Radix for 7 d. Pathological sections were prepared to observe the damages in liver, stomach, intestinal tissues in rats and detect the impacts on serum, liver, stomach and intestinal tissues and the oxidative damage index. RESULT: Compared with the blank group, all of normal administration groups and model groups showed significant damages in liver, stomach and intestinal tissues. Compared with the model groups, all of normal administration groups revealed notable alleviation in damages. Compared with the blank group, the model groups showed significant increases in AST, ALT and MDA in serum and liver (P < 0.01) and a significant decrease in GSH in serum and liver, stomach, intestinal tissues (P < 0.01). Compared with the blank group, the results showed significant decreases in ALT, AST in serum and ALT in liver in model low, medium and high dose groups and AST activity in liver tissues in the normal high dose group (P < 0.05, P < 0.01); significant decreases in GSH in serum and stomach tissues in normal low, medium and high dose groups and GSH content in liver and intestinal tissues in normal medium and high dose groups (P < 0.05, P < 0.01); notable rises in MDA in liver tissues in normal low, medium and high dose groups and MDA content in serum and stomach and intestinal tissues in normal medium and high dose groups (P < 0.05, P < 0.01). Compared with model groups, data revealed significant decreases in ALT, AST in serum in model low, medium and high dose groups, AST in liver tissues of model medium and high dose groups and ALT activity in liver in the model high dose group (P < 0.05, P < 0.01); significant increases in GSH content in serum and stomach tissues of model low, medium and high dose groups, GSH in liver tissues in model medium and high dose groups and GSH in intestinal tissues in the high dose groups (P < 0.05, P < 0.01); and notable declines in MDA content in serum in model low, medium and high dose groups, MDA in liver tissues of model medium and high dose groups and MDA in stomach and intestinal tissues the high dose group (P < 0.05, P < 0.01). CONCLUSION: According to the study, vinegar-processed Kansui Radix showed a significant lower toxicity liver, stomach, and intestines of cancerous ascites model rats, which provided a basis for clinical safe application of vinegar-processed Kansui Radix based on symptom-based prescription theory.