Analysis of Adverse Reactions in the Treatment of COVID-19 with Three Chinese Patent Medicines and Three Herbal Formulas

Objective To explore the rules and characteristics of the adverse drug reactions(ADRs)of three Chinese patent medicines and three herbal formulas for the treatment of COVID-19,and to provide a reference for clinical safe medication.Methods The cases and ADR reports of the three Chinese patent medicines and three herbal formulas in PubMed,Web of Science,Springer Link,CNKI,Wanfang and VIP database were retrieved from December 2019 to May 2021.Then we extracted and analyzed the effective information included in the literature.Results and Conclusion According to the pre-developed retrieval plan,a total of 136 documents were obtained,and a total of 6 documents met the inclusion criteria finally.553 patients used three Chinese patent medicines and three herbal formulas,and there were 133 cases of adverse reactions.The adverse reactions of patients taking the three Chinese patent medicines and three herbal formulas can all be explained under the theory of traditional Chinese medicine,and the adverse reactions can be eliminated by adding or subtracting the flavor of the medicine or stopping the medicine.

Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19:A systematic review and meta-analysis of the Chinese population

Background The coronavirus disease 2019(COVID-19)continues to spread worldwide.Integrated Chinese and Western medicine have had some successes in treating COVID-19.Objective This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas(3-drugs-3-formulas)in patients with COVID-19.Search strategy Relevant studies were identified from 12 electronic databases searched from their establishment to April 7,2022.Inclusion criteria Randomized controlled trials(RCTs),non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19.The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment.The control group was treated with conventional treatment.Data extraction and analysis Two evaluators screened and selected literature independently,then extracted basic information and assessed risk of bias.The treatment outcome measures were duration of main symptoms,hospitalization time,aggravation rate and mortality.RevMan 5.4 was used to analyze the pooled results reported as mean difference(MD)with 95%confidence interval(CI)for continuous data and risk ratio(RR)with 95%CI for dichotomous data.Results Forty-one studies with a total of 13,260 participants were identified.Our analysis suggests that compared with conventional treatment,the combination of 3-drugs-3-formulas might shorten duration of fever(MD=–1.39;95%CI:–2.19 to–0.59;P<0.05),cough(MD=–1.57;95%CI:–2.16 to–0.98;P<0.05)and fatigue(MD=–1.36;95%CI:–2.21 to–0.51;P<0.05),decrease length of hospital stay(MD=–2.62;95%CI–3.52 to–1.72;P<0.05),the time for nucleic acid conversion(MD=–2.92;95%CI:–4.26 to–1.59;P<0.05),aggravation rate(RR=0.49;95%CI:0.38 to 0.64;P<0.05)and mortality(RR=0.34;95%CI:0.19 to 0.62;P<0.05),and increase the recovery rate of chest computerized tomography manifestations(RR=1.22;95%CI:1.14 to 1.3;P<0.05)and total effectiveness(RR=1.24;95%CI:1.09 to 1.42;P<0.05).Conclusion The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19.No severe adverse events related to 3-drugs-3-formulas were observed.Hence,3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients.Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula.

The Chinese Herbal Formula Weichang’an Reduces the Proliferation of Human Gastric Cancer Cells via Mitochondrial Apoptosis

Objective The aim of the study was to investigate the effects of Chinese herbal formula Weichang’an(WCA)on the proliferation and mitochondria-mediated apoptosis of human gastric cancer cells.Methods Cell Counting Kit-8(CCK8)was used to evaluate the antiproliferative activity ofWCA on MKN45 cells;Giemsa staining was used to investigate cell colony formation;flow cytometry was used to analyze cell cycle,apoptosis rate,and caspases activation;and Hoechst staining was used to analyze the morphology of cell nuclei.The mitochondrial membrane potential was analyzed by both flow cytometric measurements and fluorescence microscopy.Western blot was used to analyze the protein levels of pro-caspase-3,Bcl-2,Bax,and Bcl-X.MKN45 cells were subcutaneously injected into the right forelimb of 16 nude mice to establish the tumor xenograft model,and a total of 12 nude mouse tumor xenograft models were successfully created.The nude mice were divided into the control group and the WCA-treated group.The two groups received normal saline and WCA treatment at 35.49 g/kg by a single daily oral gavage for 21 days.The body weight and tumor size of the nude mice were measured twice a week.The ultrastructural changes of subcutaneous tumors were observed by a transmission electron microscope.Results WCA can suppress cell proliferation and colony formation.It can also induce changes in the mitochondrial membrane potential and increase the activities of caspases-3,caspases-8,and caspases-9 in MKN45 cells.WCA induced S-phase arrest and apoptosis in MKN45 cells,and decreased the expression levels of antiapoptotic proteins Bcl-2 and Bcl-X in MKN45 cells,while increasing the expression levels of the proapoptotic proteins Bax and pro-caspase-3 compared with the control group.WCA inhibited the growth of a xenografted MKN45 tumor in nude mice,and the protein levels of Bax and pro-caspase-3 were significantly increased,while Bcl-X and Bcl-2 were reduced compared with the control group.The differences are statistically significant(p<0.05).Conclusion WCA could suppress the proliferation of gastric cancer cells via mitochondrial apoptosis.

Classical Chinese Herbal Formulas in the Treatment of Coronary Heart Disease: A Narrative Review

Objective:To summarize the current evidence for 8 frequently prescribed Chinese herbal formulas(CHF)as treatments for angina pectoris in patients with coronary heart disease(CHD)and the associated adverse reactions.Methods:Seven electronic databases were screened from their inception through July 2018 for all evidence related to classical CHF for the treatment of patients with CHD.Results:CHF improves CHD outcomes in terms of angina pectoris,electrocardiogram results,Chinese medicine syndromes and biomarkers iomarkers.The combination of CHF and Western medicine(WM)is more effective on CHD than WM alone.The use of CHF to treat CHD shows the same or better clinical effects as the use of WM alone.The 8 investigated CHF do not induce hepatic and renal toxicity or other serious adverse effects.Conclusions:The safety and efficacy of 8 frequently prescribed herbal formulas for treating CHD have been confirmed in many studies.The findings of these studies are positive but should be interpreted cautiously due to the poor methodological quality of the randomized controlled trials(RCTs)and meta-analyses.Additional high-quality,multi-center,large-sample RCTs should be performed to confirm these results.

Jianqu,a traditional Chinese medicine,alleviates functional dyspepsia in high-calorie and high-protein diet mice

Background:Jianqu has been used to alleviate symptoms in patients with functional dyspepsia,but its specific anti-functional dyspepsia effect is still unclear.Therefore,our study aimed to investigate the impact of Jianqu on functional dyspepsia in mice.Methods:The phytochemical profile of Jianqu was analyzed by UPLC-Q-TOF-MS.Subsequently,Kunming mice were fed a high-calorie or high-protein diet(HCHP)for 7 days,and then orally treated with vehicle or Jianqu(1.62 g/kg body weight(b.w.)and 3.25 g/kg b.w.)for 10 days.A carbon powder solution was used to detect the gastric emptying and intestinal transit rate.The pathological changes in stomach and duodenum were evaluated by hematoxylin-eosin staining.The occludin,claudin-1,ZO-1 and CD45 expression was measured by immunocytochemical staining.Importantly,the serum gastrointestinal hormones were detected by ELISA.In addition,the gut microbiota composition was determined using 16S rRNA gene sequencing.The cecal short chain fatty acids were assessed by gas chromatography.Results:In general,17 phytochemical compounds were identified from Jianqu,which significantly improved the gastric emptying rate and intestinal transit rate(p<0.01),increased the body weight and food intake(p<0.0001)in HCHP mice as well.Though HCHP did not cause significant pathological lesions in the gastrointestinal tract,increased the expression of CD45 in the duodenum(p<0.05)was observed.Notably,Jianqu attenuated this abnormal expression of CD45(p<0.05).The levels of serum gastrointestinal hormones were significantly normalized by Jianqu intervention(p<0.05).Moreover,Jianqu increased the relative abundance of Roseburia as well as short chain fatty acids levels in cecum(p<0.05).Conclusion:The present results showed that Jianqu alleviated dyspeptic symptoms in HCHP mice possibly through reducing the duodenal leukocyte infiltration,and regulating the expression of gastrointestinal hormones.These effects may be partly related to the increasing cecal short chain fatty acids levels probably via gut microbial modulation.

Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.

Formula and Pharmacological Identification of Diarrhea Arresting and Dysentery Treating Dietary Traditional Chinese Herbal Medicine for Livestock

This study was aimed to develop the Chinese herbal formula with dysentery arresting and antidiarrheal effect. [Method] The Chinese herbal for-mulation was used to carry out the clinical curative effect test and pharmacological test for il livestock. [Results] Curative effect test showed that the formula had good effect on abdominal pain, diarrhea and fecal changes of livestock, and the cure rate reached up to 92%. Pharmacological experiments showed that the formula had sig-nificant inhibitory effect on the gastrointestinal motility of the tested animals, and the diarrhea arresting and dysentery treating effect of the formula was also extremely significant. In addition, the formula was safe for tested animals, proving to be reli-able. [Conclusion] The formula has distinct curative effect on treating white scour of piglets, yel ow scour of piglets, livestock gastroenteritis and lienteric diarrhea, and it can also be used in veterinary clinic, as wel as be used as feed additive.

Chinese herbal formula shen-ling-bai-zhu-san to treat chronic gastritis: Clinical evidence and potential mechanisms

BACKGROUND Chronic gastritis(CG) is an inflammatory disease of the gastric mucosa. Shenling-bai-zhu san(SLBZS), a traditional Chinese medicine formula, is widely used for treating CG. Nevertheless, its effects are currently unclear.AIM To determine the clinical evidence and potential mechanisms of SLBZS for the treatment of CG.METHODS We systematically searched 3 English(PubMed, Embase, Medline) and 4 Chinese databases(Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform,and the VIP information resource integration service platform) without language or publication bias restriction. Qualified studies were selected according to pre-set inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis and literature quality assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the quality of evidence. And then, network pharmacology analysis was applied to primary research the mechanisms of action of SLBZS on CG.RESULTS Fourteen studies were finally included, covering 1335 participants. Meta-analysis indicated that:(1) SLBZS was superior to conventional therapies [risk ratio(RR):1.29, 95% confidence interval(CI): 1.21 to 1.37, P < 0.00001];(2) SLBZS was better than conventional therapies [RR: 0.24, 95% confidence interval(95%CI): 0.11 to 0.55, P = 0.0007] in terms of recurrence rate and reversal of Helicobacter pylori positivity(RR: 1.20, 95%CI: 1.11 to 1.30,P < 0.00001);and(3) The safety of SLBZS for CG remains unclear. According to the GRADE method, the quality of evidence was not high. Besides, SNZJS might treat CG by acting on related targets and pathways such as EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, and others.CONCLUSION SLBZS might be useful in treating CG, but long-term effects and specific clinical mechanisms of it maintain unclear. More samples and high-quality clinical experiments should be assessed and verified in the next step.

Therapeutic Actions of the Chinese Herbal Formulae with Cold and Heat Properties and Their Effects on Ultrastructures of Synoviocytes in Rats of the Collagen-Induced Arthritis

The therapeutic actions of Qing Luo Yin (QLY清络饮) with heat property and Wen Luo Yin (WLY温络饮) with cold property on pain, swelling of the ankle, arthritis index and ultrastructures of synoviocytes were compared in rats of type II collagen-induced arthritis (CIA), with tripterygium glycosidorum (TG) used as control. The results indicated that both QLY and WLY could reduce pain, swelling of the ankle and the arthritis index of CIA, and QLY had better effects in reducing the swelling of the ankle and controlling the secondary pathological lesions as compared with WLY. Investigation on the ultrastructures of synoviocytes indicated that both QLY and WLY could reduce the number of Golgi apparatus, rough surface endoplasmic reticulum, dense bodies, matrix filaments and vacuoles so as to suppress the excessive secretion of synoviocytes in rats of CIA.

Chinese herbal formula Tongluo Jiunao injection protects against cerebral ischemia by activating neurotrophin 3/tropomyosin-related kinase C pathway

The Chinese herbal formula Tongluo fiunao, containing the active components Panax notogin- seng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control （Xuesai Tong, containing Panax notoginseng） or saline intraperitoneally to investigate the pathway involved in the action of TongIuo fiunao injection. 2,3,5-Triphenyltetrazolium chloride （TTC） staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo fiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo fiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/ tropomyosin-related kinase C pathway.

Chinese herbal formulae defend against Mycoplasma gallisepticum infection

Mycoplasma gallisepticum HS strain(MG-HS)is a pathogen that causes chronic respiratory disease(CRD)in chicken,which is characterized by host respiratory inflammatory damage,brings huge economic losses to the poultry industry.Recently,emerging Chinese herbal medicines(CHM)have been used to treat CRD.This study was aimed to investigate the preventive and therapeutic effects and their potential mechanisms of Chinese herbal medicinal formulae(CHMF),which consisted of 10 kinds of Chinese herbal medicine including Scutellaria,Houttuynia cordate and licorice,on MGinduced CRD in chickens.With respect to the preventive effect,the results showed that CHMF could effectively recover the MG-induced decrease on body weight and feed conversion ratio.Histopathological analysis showed that both prevention and treatment of CHMF could significantly alleviate the severe respiratory inflammation induced by MG infection.Moreover,compared with the MG infection group,both the prevention groups and the treatment groups of CHMF could effectively reduce the expression of MG adhesion protein(p MGA1.2)to inhibit the proliferation of MG,and thus effectively inhibit the expression of MG-induced inflammatory factors interleukin-1β(IL-1β)and tumour necrosis factor-α(TNF-α).In summary,these findings confirm that CHMF can protect chickens from various tissue damage caused by MG infection and has no adverse effects on the performance of chickens in the short term.And its efficacy against MG is equal to or better than that of tiamulin.

Fetal bovine serum versus Chinese herbal formula Naoluoxintong serum supplementation for proliferation and differentiation of rat embryonic neural stem cells

BACKGROUND： How to induce endogenous neural stem cells （NSCs） to differentiate into needed neural cell types is a hot spot of current researches. OBJECTIVE： To compare differences between fetal bovine serum and Chinese herbal formula Naoluoxintong serum supplementation for inducing proliferation and differentiation in rat embryonic NSCs. DESIGN, TIME AND SETTING： An in vitro, serum pharmacology, comparative, observation study was performed from March to September in 2008 at the Laboratory of Neurodegenerative Diseases, College of Life Science in University of Science and Technology of China, the Key Laboratory Breeding Base of Acupuncture Foundation and Technology in Anhui University of Traditional Chinese Medicine, the Anhui Province Key Laboratory of R ＆ D of Chinese Medicine, and at the Level 3 Laboratory of Molecular Biology of the State Administration of Traditional Chinese Medicine. MATERIALS： The Chinese herbal formula Naoluoxintong was produced by Radix Astragali, Radix Notoginseng, Rhizoma Chuanxiong, Scolopendra at Anhui University of Traditional Chinese Medicine. Mouse anti-rat nestin, gliat fibrillary acidic protein, and galactocerebroside monoclonal antibodies, as well as rabbit anti-neuron-specific enolase polyclonal antibody were produced by Chemicon, Billerica, MA, USA. METHODS： Wistar rats aged 3 months were intragastrically infused with Naoluoxintong. Wistar rat embryonic NSCs （passage 8） were induced to proliferate and differentiate using 10% fetal bovine serum, 10% Naoluoxintong serum, and 10% rat serum. MAIN OUTCOME MEASURES： Phenotypic changes in cultured cells were detected using phase contrast microscopy, and cell proliferation and differentiation were observed using immunofluorescence staining. RESULTS： Proliferation and differentiation of embryonic NSCs was induced by three different types of blood serum. Although the differentiation time course with Nao/uoxintongserum was later than with the other two methods, the differentiated cells were morphologically similar to mature neurons to a greater extent. CONCLUSION： Nao/uoxintong serum supplementation induced differentiation of NSCs into neuronal-like cells and stimulated neuronal maturation.

Effects of Fujian tablet on Nogo-A mRNA expression and plasticity of the corticospinal tract in a rat model of focal cerebral ischemia

The present study investigated the effects of Fujian tablet, a Chinese medicine compound that can nourish liver and kidney, on corticospinal tract plasticity and cervical cord microenvironment in rats with focal cerebral ischemia. Results showed that motor function of rats with right proximal middle cerebral artery occlusion was significantly improved following treatment with Fujian tablet, 9 g crude drug/kg. Anterograde tracing revealed significantly increased biotinylated dextran amine expression in the denervated （left） side of the cervical cord （C4-6） following Fujian tablet treatment, and significantly decreased Nogo-A mRNA expression was detected in the denervated side of the cervical cord （C4-6） using in situ hybridization. Pearson＇s correlation analysis showed a negative correlation between biotinylated dextran amine and Nogo-A mRNA expression （r = -0.943, P 〈 0.01）. Results demonstrated that Fujian tablet can promote corticospinal tract plasticity possibly through the inhibitory effect on Nogo-A mRNA expression in the cervical spinal cord, thereby improving motor dysfunction.

Potential mechanism of Huatan Qushi decoction on improving phlegm-dampness constitution using microRNA array and RT-qPCR targeting on hsa-miR-1237e3p

Background:Metabolic diseases pose considerable burden on the healthcare system worldwide,indicating the significance of prevention and treatment.In constitution theory of traditional Chinese medicine,phlegm-dampness constitution(PDC)is the common basis of metabolic diseases.In clinical practice,Huatan Qushi(HTQS)decoction targeting on PDC can effectively improve metabolic indicators.However,its underlying biochemical mechanism still remains unclear.Methods:Eight PDC participants received HTQS decoction for three months.Their blood was collected at baseline and 1 and 3 months after intervention started.Related biomedical indicators were detected.High-throughput sequencing and RT-qPCR were used for validation.Due to the missing data,repeated measures with missing values in mixed models were used.Results:After 3-month treatment,HDL-C level increased(P<.001)and FBG,FINS,and HbA1c all showed decreasing trend at different time points(all P<.05).After miRNA high-throughput sequencing,compared with the baseline,differential miRNAs at 1 and 3 months were screened,and target gene prediction and KEGG pathway enrichment analysis were performed.The results displayed that metabolic disease-related pathways mainly included pathways in cancer,PI3K-Akt signaling pathway,etc.Further,RT-qPCR showed that hsa-miR-1237e3p differed statistically(P=.008).Then we validated the target genes of hsa-miR-1237e3p in the“Pathways in Cancer”pathway including SDF1,AC,CRK,and HGF,also known as upstream target genes of PI3K/AKT pathway.The results showed that two indicators of CRK and HGF were in statistical significance(P=.045 and P=.036,respectively).Conclusion:PDC serves as a common basis for various metabolic diseases.Through adjusting PDC,HTQS decoction can improve biomedical indicators including blood glucose,HbA1c,insulin,and HDL-C.The target pathway is“Pathways in cancer”.Specifically,HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237e3p,and probably exerts effects on their downstream PI3K/AKT pathway.

Efficacy of integrative medicine in deficiency of both qi and yin in the rat model of type 2 diabetes

Objective:To establish a rat model of type 2 diabetes(T2DM)manifesting the Chinese medicine syndrome pattern of both qi and yin deficiency for evaluating the efficacy of a Chinese herbal formula(CHF),integrative medicine(IM),and pioglitazone(PIO)on T2DM indicators in the animal model.Methods:The rat model was induced by a high-fat diet(HFD)and streptozotocin(STZ,30 mg/kg).CHF(3.4 g/kg),PIO(2.7 mg/kg),and IM(3.4 g CHF+2.7 mg PIO)were administered to rats once daily for 14 days.Related laboratory parameters were observed.Results:Diabetic rats showed unsmooth fur,alopecia,reduced activity,huddling,somnolence,depression,pale or reddened tongue,damp/dark red tail,and high levels of water and food intake,urine volume,and stool weight,but weakened grip strength.Low levels of serum SOD,Nat-Kt-ATPase,cAMP/cGMP,and a high level of iNOS were observed.Hyperglycemia,hyperinsulinemia,insulin resistance,high levels of serum glucagon/IDE and pancreatic amylin,and low serum and pancreatic SS levels were evident as well.Conclusions:A rat model of T2DM with both qi and yin deficiency was successfully replicated.CHF appeared to be more efficacious than IM and PIO in the rat model of qi and yin deficiency pattern of T2DM,though IM and PIO were each found to have their merits and drawbacks in attenuating T2DM indicators in the rat model.

A Yang-invigorating compound mixture alters neurotransmitters in rat telencephalon after exercise-induced fatigue

The aim of this study was to observe the changes in monoamine and amino acid neurotransmitters in the telencephalon of rats at four functional states after exhaustive exercise and treatment with a Yang-invigorating compound recipe.The main components of this Chinese traditional medicine preparation included Radix Ginseng,Rhizoma Chuanxiong,Fructus Schisandrae,Cortex Cinnamomi,Cornu Cervi Pantotrichum,Radix Morindae Officinalis,and Gecko.This experiment showed that dopamine（DA）,5-hydroxyindole acetic acid（5-HIAA）,and γ-aminobutyric acid levels noticeably decreased,while DA/5-hydroxytryptamine（5-HT） increased.Furthermore,glutamate（Glu） and Glu/γ-aminobutyric acid significantly increased after 1 hour of exercise in rats in the exercise ＋ medication group.The 5-HT and 5-HT/5-HIAA levels noticeably decreased,and DA/5-HT and Glu levels showed a robust and significant increase immediately after exhaustive exercise.The 5-HT,5-HT/5-HIAA levels sharply decreased,while DA/5-HT,Glu and γ-aminobutyric acid levels increased at 12 hours after exhaustion recovery.The results prove that Chinese herbal formula for strengthening Yang can induce changes in neurotransmitters in the telencephalon of rats after exhaustive exercise during the recovery process,and further improve central nervous system function.

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis:A Multi-center,Double-Blinded and Randomized Controlled Trial

Objective: To assess the efficacy and safety of Bufei Jiedu(BFJD) Granules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis(MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups(1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months(6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life(QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo(58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion(5 months vs. 11 months). The cavity closure rate of the BFJD Granules group(50.6%, 43/85) was higher than that of the placebo group(32.1%, 26/81;P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group(all P<0.01). Overall, the death rates in the two groups were not significantly different;5.1%(8/156) in the BFJD Granules group and 2.6%(4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rate, and rapidly improved QoL of patients with MDR-PTB(Registration No. ChiCTR-TRC-12002850)

Seropharmacological Study on Osteogenic Effects of Post-Absorption Ingredients of An Osteoprotective Herbal Formula

Objective： To further investigate the in vitro effects of an osteoprotective herbal formula ＂ELP＂ （Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psora/eae） using seropharmacological approach. Methods： Rats were fed with ELP or its individual component herbs for 2 days. The serum containing the post-absorbed ingredients of the herbal items were collected for cell culture using UMR106 cell, RAW264.7 cell and mesenchymal stem cell （MSC） isolated from the bone marrow of the rats. The effects of the herbal-containing serum on cell toxicity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay; bromodeoxyuridine assay was conducted to measure the cell proliferation of UMR106 cell and MSC; cell activity was measured using colorimetric method, and mRNA expression of runt-related transcription factor 2 （Runx2）, alkaline phosphatase （ALP） and osteopontin （OPN） of UMR106 and MSC as well as matrix metalloproteinase 9 （MMP-9）, tartrate-resistant acid phosphatase （TRAP） and cathepsin K of RAW264.7 were analyzed using real-time reverse-transcription polymerase chain reaction. Results： ELP and its component serum exhibited no cytotoxic effects on the cells. The ELP-containing serum increased the proliferation of UMR106 cell and MSC by 25.7% and 14.4%, respectively and the alkaline phosphatase activity of MSC was increased by 42.6%. On the contrary, it inhibited the RAW264.7 cell differentiation by 29.2%. ELP serum upregulated the Runx2 expression of UMR and MSC by 1.18 fold and 1.27 fold, respectively. It also upregulated ALP and OPN expression in MSC by 1.69- and 2.12-fold, respectively. On the other hand, ELP serum down-regulated MMP-9 and cathepsin K expression of RAW264.7 cell by 0.46- and 0.36-fold, respectively. Conclusions： The serum of the animals fed with ELP contains active ingredients which are effective in promoting osteogenesis and inhibiting osteoclastogenesis.

Polyherbal formula SC-E3 inhibits rheumatoid arthritis activity in a mouse model of type-Ⅱcollagen-induced arthritis

Objective:SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine.In our previous study,we demonstrated the antioxidant and anti-inflammatory effects of SC-E3.The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis(CIA).Methods:In vivo,male DBA/1 J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund’s adjuvant,to induce arthritis.SC-E3 was orally administered daily for 23 days.In vitro,bone marrow-derived macrophages(BMMs)were treated with macrophage colony-stimulating factor(M-CSF)and receptor activator of nuclear factor-j B ligand(RANKL)in the absence or presence of SC-E3.Results:Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice,as evidenced by reduced paw swelling,bone erosion and deformation,inflammatory cell infiltration,and inflammation in synovial membrane.SC-E3 also reduced serum levels of tumor necrosis factor-a,interleukin-1 b,aspartate aminotransferase and alanine aminotransferase.Furthermore,tartrateresistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice.In addition,the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3.Conclusion:These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis,and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.