Chinese Formula Research Articles

Thoughts on Coronavirus Disease 2019 Based on JingFang Medicine (Classical Chinese Formula) Solutions for COVID-19.

This article aims to provide some thoughts on the prevention and treatment of Coronavirus Disease 2019 (COVID-19) from the perspective of JingFang Medicine (Classical Chinese Formula). It is believed that the vague theoretical understanding of COVID-19 in Traditional Chinese Medicine does not hinder the precise treatment of the disease by following the rule of “With this Zheng, prescribe this Fang.” According to the principle of “Fang-Zheng Correlation” and the knowledge gained from the thousands of years of experience in treating febrile diseases, Xiao Chai Hu Decoction () and its modifications are recommended with the emphasis on individualized treatment. As another form of practicing “Fang-Zheng Correlation,” generalized group treatment should also be paid attention to. Giving considerations to the historical medical data, Jing Fang Bai Du Powder () and Shi Shen Decoction () are recommended for group prevention treatment. Assisting the Zheng (Upright) Qi and using tonic formulas are two entirely different concepts. According to the principle of “Fang-Zheng Correlation,” tonics abuse should be avoided in the prevention of COVID-19, and the using of Huang Qi ( Radix Astragali seu Hedysari) should also be very carefully done.

Research progress on antidepressant therapeutic biomarkers of xiaoyaosan

Depression is one of the most prevalent and serious mental disorders with a significant burden of disease. Xiaoyaosan (XYS), a well-known Chinese formula, has been widely used in the treatment of depression. Both clinical studies and animal experiments have indicated that XYS has an obvious antidepressant activity. How to select objective pharmacodynamic markers for traditional Chinese medicine (TCM) treatments based on clinical metabolites, linking pathogenic genes, and drug targets, is a bottleneck problem in the modernization of TCM. To address this issue, we sorted out clinical metabonomics experiments of XYS in treating depression, constructed a metabolic profile of therapeutic biomarkers, and deduced metabolic biomarker-protein interactions networks. The therapeutic biomarkers found for XYS were involved in neurotransmitter synthesis, energy metabolism, and gut microbial metabolism. This study aims to provide a scientific basis for the clinical diagnosis of depression and evaluate the efficacy of XYS in its treatment.

Advances in anti hepatic fibrotic therapy with Traditional Chinese Medicine herbal formula.

The process of liver fibrogenesis includes a number of common and etiology-dependent or independent mechanisms and events. Up to now, there are still insufficient approved biological or chemical therapies directly targeting and reversing advanced fibrosis. The key is that once liver fibrosis is triggered, it presents a complex network control model with the activation of HSCs as the core, resulting in poor efficacy of treatment. Traditional Chinese medicine (TCM) has unique advantages in treating hepatic fibrosis because of its syndrome differentiation and treatment and comprehensive pharmacological effects of multi-channel, multi-level and multi-target. However, TCM's advantages were rarely discussed as previous reviews focused on the active ingredients of TCM and single Chinese Medicine. Therefore, this paper focuses on TCM herbal formulae's pharmacological role, target and related mechanisms in the treatment of liver fibrosis. This paper will focus on the pharmacological role, target and related mechanisms of TCM herbal formulae in the treatment of liver fibrosis. We collect English literatures or Chinese literatures with English Abstract on the treatment of liver fibrosis with TCM herbal formulae from databases including PubMed, Wiley InterScience, Science Direct OnSite/Elsevier, Ovid, Excerpta Medica Database, SpringLink, CNKI and China Biomedical Literature Database. Based on previous literatures, we summarize the TCM herbal formulae with definite anti-hepatic fibrosis effects. To some extent, classical or modern TCM herbal formulae including Yinchenhao Decoction (YCHD), Xiayuxue Decoction (XYXD), Xiaochaihutang (XCHT), Yiguanjian Decoction (YGJ), Huangqi Decoction (HQD), Dahuang Zhechong Pills (DHZC), Fuzheng Huayu Formula (FZHY), Fufang Biejia Ruangan Tablets (FFBJRG), Anluo Huaxian Pills (ALHX) and Compound 861 (Cpd861) have anti-hepatic fibrosis effect both on patients with liver fibrosis and animal models with liver fibrosis. According to the principle of syndrome differentiation and treatment, Liver fibrosis patients with different syndromes are treated with different herbal formula, which increases the difficulty of clinical efficacy research. YCHD and XYXD research lack randomized and controlled clinical trials. XCHT, YGJ and HQD research has small sample sizes despite randomized and controlled clinical trials. In contrast, most modern herbal formulae have randomized and controlled clinical trials. For instance, FZHY and ALHX recently published the research results of the combination of entecavir in the treatment of patients with chronic hepatitis B liver fibrosis or cirrhosis. Compared to anti-viral treatment with entecavir alone, this method has improved the reversion rate of liver fibrosis but still needs syndrome classification therapy of TCM. TCM Herbal formulae have a good prospect in treating liver fibrosis, but its composition of multiple drugs and a wide range of targets intensify the difficulty of studying their anti-hepatic fibrosis mechanisms. Future research needs to further study the anti-hepatic fibrosis mechanisms and select corresponding TCM herbal formula to treat patients with different syndromes of liver fibrosis or the same patient with different syndromes at different stages to achieve better curative results.

Therapeutic effectiveness of Lishi Oral Liquid combined with levocetirizine in treating atopic dermatitis: A randomized double-blind placebo-controlled clinical trial

Objective: To observe the efficacy and safety of Lishi Oral Liquid (LOL), a Chinese herbs formula, combined with levocetirizine, an antihistamine drug, in patients with damp-heat atopic dermatitis (AD). Methods: A randomized double-blind placebo-controlled clinical trial was conducted. Ninety patients diagnosed with damp-heat atopic dermatitis were randomly assigned to Lishi Oral Liquid group and control group at the ratio of 1:1. Patients were given one Lishi Oral Liquid or placebo three times per day. Both groups were treated with allantoin and vitamin E cream by topical use and levocetirizine by oral administration. Patients were followed up at the second and fourth week. The primary outcome was the scoring of atopic dermatitis (SCORAD). The secondary outcomes were visual analogue scale (VAS) and dermatology life quality index (DLQI). Results: After two weeks of treatment, there were statistical differences in SCORAD between these two groups ([Formula: see text]), whereas VAS and DLQI showed no statistical differences. There were significant differences in SCORAD and VAS between two groups at the end of four weeks of treatment ([Formula: see text]). However, no significant differences were observed in DLQI after four weeks of treatment. No serious adverse event was found during this clinical trial. Conclusion: LOL combined with levocetirizine is effective and safe for damp-heat AD treatment.

Bazhu Decoction, a Traditional Chinese Medical Formula, Ameliorates Cognitive Deficits in the 5xFAD Mouse Model of Alzheimer's Disease.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with aging. There are currently no effective treatments for AD. Bazhu decoction (BZD), a traditional Chinese medicine (TCM) formula, has been employed clinically to alleviate AD. However, the underlying molecular mechanisms are still unclear. Here we found that middle- and high-doses of BZD ameliorated the behavioral aspects of 5xFAD transgenic mice in elevated plus maze, Y maze and Morris water maze tests. Moreover, BZD reduced the protein levels of BACE1 and PS1, resulting in a reduction of Aβ plaques. We also identified a beneficial effect of BZD on oxidative stress by attenuating MDA levels and SOD activity in the brains of 5xFAD mice. Together, these results indicate that BZD produces a dose-dependent positive effect on 5xFAD transgenic mouse model by decreasing APP processing and Aβ plaques, and by ameliorating oxidative damage. BZD may play a protective role in the cognitive and anxiety impairments and may be a complementary therapeutic option for AD.

Chinmedomics facilitated quality-marker discovery of Sijunzi decoction to treat spleen qi deficiency syndrome.

Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years. However, the quality control (QC) standards of SJZD are insufficient. Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formula rapidly. In this study, we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC. A total of 56 compounds in SJZD were characterized in vitro, and 23 compounds were discovered in vivo. A total of 58 biomarkers were related to SQDS, and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status. A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy. We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng; dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria; glycyrrhizic acid, isoglabrolide, and glycyrrhetnic acid as the q-markers of licorice; and 2-atractylenolide as the q-marker of macrocephala. According to the discovery of the SJZD q-markers, we can establish the quality standard that is related to efficacy.

Metabolite profiling of traditional Chinese medicine XIAOPI formula: An integrated strategy based on UPLC-Q-Orbitrap MS combined with network pharmacology analysis

XIAOPI formula has been approved for mammary hyperplasia treatment by National Medical Products Administration in China. However, the absorbed substances of XIAOPI formula and their influences on metabolic pathways are largely remained unknown. Liquid chromatography coupled with mass spectrometry was used to identify the substances existing in the serum. Network pharmacology was utilized to explore the underlying metabolic targets and pathways involved in. Western blotting and immunofluorescence assays were carried out for target validation. The exogenous results demonstrated 196 compounds were filtered as absorbed substances, among which 63 constituents or metabolites were tentatively identified in rat serum, and the metabolites of tanshinone II and tanshinone I were found to act as the major metabolic pathways. Subsequently, the endogenous results revealed that XIAOPI formula could significantly regulate serum biochemical indices and the bile acid secretion signaling ranks as top1 among all the involved pathways. The levels of intermediates including cholic acid, glycocholic acid, taurochenodeoxycholic acid and taurocholic acid were significantly upregulated following XIAOPI treatment, accompanied by increased expression of key enzyme CYP7A1, indicating that XIAOPI formula could accelerate the bile acid metabolism pathway. Our study presented a comprehensive metabolic profile of XIAOPI formula in vivo for the first time, and bile acid synthesis pathway might be one of the key mechanisms contributing to the pharmacological function of the formula.

BabaoDan cures hepatic encephalopathy by decreasing ammonia levels and alleviating inflammation in rats.

BabaoDan (BBD) is a famous traditional Chinese formula frequently used in TCM clinics to eliminate jaundice and treat infectious viral hepatitis. This paper assesses BBD's preventive and therapeutic effects on hepatic encephalopathy after liver cirrhosis (CHE) and acute liver failure (AHE) in rats and explains its possible mechanism of action. CHE rat model was established by injection of carbon tetrachloride (CCl4) twice a week for a total of 9 weeks and then by injection of thioacetamide (TAA) to induce hepatic encephalopathy. AHE rat model was established by injection of TAA once a day for a total of 3 days. In CHE rat model, BBD was gavaged once a day at the end of the 6th week until the experiment ended. In AHE rat model,BBD was gavaged once a day 3 days before TAA injection until the experiment ended. The preventive and therapeutic effects of BBD on brain dysfunction, as well as liver injury, pathology and fibrosis were evaluated in vivo. The role of BBD in the regulation of inflammatory factors and myeloid differentiation factor 88/Toll-like receptor 4/nuclear factor kappa-B (TLR4/MyD88/NK-κ B) pathway was detected in both liver and brain in vivo. The rat bone marrow derived macrophages (BMDMs) were activated by Lipopolysaccharide (LPS), and the role of BBD in the regulation of inflammatory factors and NK-κ B pathway were detected in vitro. In CHE rat model: BBD significantly improved the total distance as well as the activity rate of rats. BBD also improved the learning and memory abilities of rats compared with the control group. In addition, BBD effectively decreased ammonia levels and significantly decreased the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and total bile acid (TBA), as well as improved the levels of total protein (TP) and albumin (Alb). In the liver, BBD not only inhibited the gene expressions of tumor necrosis factor alpha (TNF-α), interleukini-6 (IL-6), TLR4, MyD88, and NF-κ B but also inhibited the protein expressions of TLR4, MyD88, NK-κ B and TNF-α. In the brain, BBD inhibited the gene expressions of iNOS, IL-6, TNF-α, TLR-4, MyD88, and NF-κ B, as well as inhibited the protein expressions of TLR4, MyD88, P65 TNF-α and ionized calcium binding adapter molecule 1 (Iba-1). BBD also decreased NO and TNF-α in the blood. BBD improved neurological scores, blood ammonia levels and the brain inflammatory gene expressions of iNOS, TNF-α and IL-1β. BBD also improved liver function biomarkers such as ALT, TBil, TBA, TP, ALB and inflammatory and apoptotic gene expressions of TNF-α, IL-1β, IL-6, Bax, Bcl-2, caspase-9, caspase-3 and NF-κ B. In LPS-activated rat BMDMs, BBD decreased NO and TNF-α production in BMDM culture supernatant. In addition, BBD inhibited the gene expressions of TNF-α, IL-1 β and IL-6 as well as the phosphorylation of P65. BBD can prevent and cure hepatic encephalopathy (HE) derived from both chronic and acute liver diseases. BBD can reduce hyperammonemia as well as the systematic and neurological inflammation. Inflammation is likely an important target of BBD to treat HE. The anti-inflammatory role of BBD may lie in its regulation of the TLR4/MyD88/NF-κ B pathways.

The combined effect of oleonuezhenide and wedelolactone on proliferation and osteoblastogenesis of bone marrow mesenchymal stem cells

BackgroundRegulation of the survival and differentiation of bone marrow mesenchymal stem cells is an essential consideration in the development of targeted drugs for treatment of osteoporosis. PurposeThe present study aimed to evaluate the combined effect of wedelolactone and oleonuezhenide, two compounds from Chinese formula Er-Zhi-Wan, on osteoblastogenesis and the underlying molecular mechanisms. MethodsMTT assay was taken to evaluate cell proliferation. The alkaline phosphatase (ALP) activity assay was used to determine the activity of ALP. Alizarin red S (ARS) staining was taken to indicate the intensity of the calcium deposits. Quantitative real-time PCR and Western blot were performed to the levels of Runx2, Osteocalcin, and Osterix expression in mouse bone marrow mesenchymal stem cells (BMSCs). Ovariectomized mouse model and bone histomorphometric analysis were also used to research the effects of wedelolactone and oleonuezhenide on bone loss caused by ovariectomy. ResultsWedelolactone combined with oleonuezhenide enhanced osteoblast differentiation and bone mineralization. Osteoblastogenesis-related marker genes including osteocalcin, Runx2, and osteorix were upregulated in the presence of wedelolactone and oleonuezhenide. At the molecular level, oleonuezhenide did not affect GSK-3β phosphorylation induced by wedelolactone, but elevated casein kinase 2-alpha (CK2α) expression, resulting in β-catenin and Runx2 nuclear translocation. In addition, 30 µM wedelolactone-induced cytotoxicity in bone marrow mesenchymal stem cells was relieved by 9 µM oleonuezhenide. These cells were protected by oleonuezhenide and maintained osteoblastic activity. Oleonuezhenide increased Wnt5a and CK2α expression. Wedelolactone-reduced extracellular signal-regulated kinase (ERK) phosphorylation was reversed by oleonuezhenide. In ovariectomized mice, administration of wedelolactone and oleonuezhenide prevented ovariectomy-induced bone loss by enhancing osteoblastic activity. ConclusionThese results suggested that oleonuezhenide enhanced the effects of wedelolactone on osteoblastogenesis. These two compounds could be developed as a combined therapeutic agent for osteoporosis.

Baihe Zhimu formula attenuates the efficacy of tamoxifen against breast cancer in mice through modulation of CYP450 enzymes

BackgroundMajor depression is an important complication in patients with breast cancer, but is an underrecognized and undertreated condition in this population. The Baihe Zhimu Tang (BZ formula) is a traditional Chinese formula consisting of Lilium brownii var. viridulum Baker (L. brownii) and Anemarrhena asphodeloides (A. asphodeloides) Bunge that is used for the treatment of depression. However, the interaction between tamoxifen and BZ formula is frequently overlooked by traditional and alternative medical doctors. In the present study, the influence of BZ formula on the effectiveness of tamoxifen in breast cancer in mice and the effects of tamoxifen on the antidepressant effect of BZ formula and its major components mangiferin and timosaponin BII in mice were investigated.MethodsIdentification of the major components of BZ formula was performed using fast HPLC-tandem mass spectrometry (HPLC-MS/MS). The main flavonoids and saponins in A. asphodeloides were determined by HPLC-UV and HPLC-ELSD, separately. The antidepressant efficacy of BZ formula was evaluated using a mouse tail-suspension test. The effects of BZ formula on the antineoplastic activity of tamoxifen were performed in a mouse xenograft model of human breast cancer MCF-7 cells. P450 activity was determined using microsomal incubations by HPLC-MS/MS. Measurement of serum concentrations of tamoxifen and its metabolites was used by HPLC-MS/MS.ResultsBZ formula attenuated the effectiveness of tamoxifen treatment of breast cancer and reduced the concentrations of endoxifen and 4-OH-tamoxifen in tumor-bearing mice. Of two of the major components of BZ formula, the antidepressant effect of mangiferin, but not timosaponin BII, was significantly inhibited by tamoxifen in mice. BZ formula and its component mangiferin also significantly inhibited CYP450 enzyme activity in rat liver microsomes.ConclusionBZ formula attenuated the effectiveness of tamoxifen in treatment of breast cancer in mice by influencing CYP450 enzymes. The present study laid a foundation for the treatment of patients with breast cancer and depression by BZ formula or other Chinese herbal formulas containing A. asphodeloides.

Geo-herbalism study of Magnoliae Officinalis Cortex

Magnoliae Officinalis Cortex( MOC),the stem bark of Magnolia officinalis( MO) and M. officinalis var. biloba( MOB),is a main ingredient in more than 200 types of Chinese formulae commonly used in clinics. MO and MOB are widely distributed in China,from Sichuan of the west to Zhejiang province of the east and from Shannxi province in the north to Guangxi province in the south. This review summarizes new findings on geo-heralism of MOC concerning textual research,plants taxonomy,genetic study,chemical study,and pharmacological activity,resulting in the following views. ①The original plants of MOC are suggested to be divided into three geographic clans according to the form of leave and the result of genetic research; ②Concentrations of magnolol,honokiol,magnoloside A,magnoloside B,magnoflorine,and β-eudesmol in samples collected from different geographic areas are varied;③Samples of MOC produced in Hubei and Sichuan were traditionally regarded as Dao-di herbs,which were called Chuanpo,and the pure haplotype of MOC produced in Hubei may become a genetic index.

Comparative effectiveness of six Chinese herb formulas for acute exacerbation of chronic obstructive pulmonary disease: a systematic review and network meta-analysis

BackgroundSix Chinese herb formulas, namely, the Weijing decoction (WJ), the Maxingshigan decoction (MXSG), the Yuebijiabanxia decoction (YBBX), the Qingqihuatan decoction (QQHT), the Dingchuan decoction (DC) and the Sangbaipi decoction (SBP), are commonly used, along with routine pharmacotherapy, to manage the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In this study, we conducted a systematic review to summarize the efficacy of these six formulas, and we also conducted a network meta-analysis (NMA) to rank these formulas.MethodsWe searched five English databases and four Chinese databases, with dates ranging from the starting dates of these databases to December 2016. Randomized controlled trials that evaluated any of the six Chinese herb formulas combined with the use of pharmacotherapy for AECOPD were identified.ResultsFifty-five studies involving 4560 participants were included. The pairwise meta-analyses showed that WJ and QQHT had superior effects on the improvement of lung function (forced expiratory volume in 1 seconds; FEV1) (mean difference (MD): 0.25, 95% confidence interval (CI): 0.19–0.30 and 0.34, 95%CI: 0.10–0.58). MXSG, WJ and QQHT were found to be more effective for improving arterial blood gases (PaO2 and PaCO2). In terms of effective rates, all of these formulas had additional favourable effects compared to routine pharmacotherapy. The results of the NMA analyses indicated that only MXSG showed superior add-on effects for the improvement of FEV1 (MD: 0.37, 95% credible interval (CrI): 0.03–0.72). Most of the formulas combined with routine pharmacotherapy were superior to pharmacotherapy alone for the improvement of arterial blood gases and effective rates. The ranking tests suggested that QQHT and MXSG combined with routine pharmacotherapy might be optimal options for the treatment of AECOPD.ConclusionsThis NMA indicated that QQHT and MXSG might be more effective treatment regimens for AECOPD. Further well-designed studies that specifically examine the direct comparisons of these formulas are needed to support our conclusions.

Integrating network pharmacology and bioinformatics analysis to explore the mechanism of Yupingfengsan in treating lung adenocarcinoma

IntroductionYupingfengsan (玉屏风散) is a classical traditional Chinese formulae with proven therapeutic effect on the disease of respiratory system. However, its action mechanism remains obscure for lung adenocarcinoma (LAD). This study aimed to investigate the potential target genes and the mechanism of Yupingfengsan in the treatment of LAD. MethodsYupingfengsan chemical ingredients and related targets were predicted by public databases. Differential expression genes of LAD were obtained from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was used to execute gene ontology function and pathway enrichment analysis. The protein interaction network was constructed by Cytoscape. Finally, potential target genes and mechanism of Yupingfengsan on LAD were predicted. The differential expression and prognostic analysis of target genes were verified by TCGA database and the Kaplan-Meier plotter, respectively. ResultsA total of 253 targets from 30 active ingredients of Yupingfengsan were predicted. 4426 DEGs were identified from TCGA LAD data sets. 32 upregulated and 52 downregulated genes were obtained between Yupingfengsan putative targets and DEGs of LAD. MAPK, VEGF, and ErbB signaling pathways seemed to be the most likely mechanism. 6 potential target genes, PLA2G4A, PRKCB, PIK3R1, KDR, PLA2G1B and PTGS2 were extracted. These 6 candidates were verified significantly different expression between LAD and paired adjacent normal tissues, and PRKCB, PIK3R1, KDR, PLA2G1B suggested a significant correlation with LAD prognosis. ConclusionDifferentially expressed in tumors, PLA2G4A, PRKCB, PIK3R1, KDR, PLA2G1B and PTGS2 are potential therapeutic targets of Yupingfengsan in the treatment of LAD, and MAPK, VEGF and ErbB signaling pathways are involved.

Society for Acupuncture Research 2019: Putting the Whole Acupuncturist Back Together Again-To Set Them to Work!

Society for Acupuncture Research 2019: Putting the Whole Acupuncturist Back Together Again-To Set Them to Work!

Danhong Injection Attenuates High-Fat-Induced Atherosclerosis and Macrophage Lipid Accumulation by Regulating the PI3K/AKT Insulin Pathway.

High-fat diet (HFD) is reported to induce atherosclerosis and insulin resistance. Macrophage lipid accumulation has been implicated as key mediators during the development of HFD-induced atherosclerosis. Traditional Chinese formula, which has long been used to improve disorder of glucose and lipid metabolism of patients, is now gradually being used as complementary therapy. This study aimed to investigate the effect of Danhong injection (DHI), a Chinese medicine used for the treatment of coronary artery disease, on atherosclerosis and its underlying mechanisms. We observed the effects of DHI on HFD-induced atherosclerosis in a mice model, macrophage lipid accumulation in an ox-LDL-stimulated macrophage model, and the role of PI3K/AKT insulin pathway in the process of DHI ameliorating atherosclerosis. The data demonstrated that DHI attenuated atherosclerosis by ameliorating blood lipids, reducing the atherosclerotic index and atherosclerotic plaque area in HFD-induced atherosclerotic mice, and inhibiting TC levels in an ox-LDL-induced macrophage model. By estimating the levels of serum insulin resistance-related indexes and protein expression of GLUT-4, DHI treatment dramatically inhibited the levels of fasting serum NEFA and fasting serum insulin and promoted the protein expression of GLUT-4 in aortas of the HFD-induced atherosclerotic mice. Moreover, according to the hints provided by microarray-based transcriptional profiling, the results demonstrated that DHI treatment also promoted the activation of PI3K/AKT insulin signaling pathway induced by IRS-1 in aortas of HFD-induced atherosclerotic mice. Furthermore, in an ox-LDL-induced macrophage model, the activation of PI3k/AKT signaling pathway also effectively functioned in the process of DHI inhibiting macrophage lipid accumulation. These results highlight that DHI treatment attenuates atherosclerosis and macrophage lipid accumulation by promoting the activation of PI3K/AKT insulin signaling pathway. It provides new insights into the molecular mechanism of DHI and its therapeutic potential in the treatment of atherosclerosis.

Abstract 1855: Re-purposing traditional Chinese anti-asthma formula ASHMI for triple negative breast cancer

Abstract Breast cancer is the most common cancer among women worldwide, contributing to 25.4% of newly diagnosed cancer cases in 2018. Triple negative breast cancer (TNBC) accounts for 10-20% of the breast cancer cases and represents an unmet clinical need because of its higher risk of recurrence and metastasis. Adjuvant therapies have often been employed to prevent secondary recurrence. Traditional Chinese medicine (TCM) formulations have long been used in prevention and cure of many types of diseases because of its anti-inflammatory property. Mainstream treatment modalities for TNBC involve surgery, radiation and chemotherapy (adjuvant or neoadjuvant). Unfortunately, chemotherapy in these patients often lead to resistance, which underscores the importance of alternative therapeutic approaches for this cancer. To this end, we wanted to evaluate anti-carcinogenic property of a TCM formulation ASHMITM developed primarily for asthma treatment. ASHMI™ is an extract of 3 traditional Chinese medicinal herbs-Ganoderma lucidum (Ling-Zhi), Sophora flavescens Ait (Ku-Shen) and Glycyrrhiza uralensis Fischer (Gan-Gao). For this study, triple-negative/basal B mammary carcinoma cell line MDA-MB157 was treated with two different concentrations of ASHMI and cellular proliferation was examined by [3H] thymidine incorporation assay. ASHMITM treated cells showed approximately 74% less [3H] thymidine incorporation indicating dampened proliferation. This observation was validated using western blot analysis with whole cell lysate, showing reduced expression of proliferation markers PCNA and NFκB. Interestingly, an increased expression of tumor suppressor protein cyclin-dependent kinase inhibitor 1 C (p57, Kip2) was observed after ASHMITM treatment. Next, we tested anti-proliferative property of the individual constituents and observed Ganoderma lucidum (GL) extract had a comparable efficacy as the whole formulation at a concentration of 100μg/ml. This observation was further confirmed by western blot and the same expression pattern was observed for PCNA, NFκB and p57. GL was further fractionated into 11 sub-components and each component was tested for the their anti-proliferative activity using similar assays. Fraction 2 with Ganoderenic acid D showed dose-dependent inhibition of cell proliferation and was further tested for its activity at lower concentrations. Ganoderenic acid D had similar efficiency as 100μg/ml of whole GL extract at a concentration as low as 2.5μg/ml suggesting this active compound might be primarily responsible for the anti-proliferative effect of GL. Our studies using an anti-inflammatory formulation of TCM have identified an active anti-carcinogenic compound, Ganoderenic acid D, that could be potentially used as an adjuvant in TNBC therapies. Citation Format: Sanjukta Chakraborty, Fei Mo, Martin Walsh, Changda Liu, Mingzhuo Cou, Rachana Maniyar, Ghada Ben Rahoma, Sarnath Singh, Tara Jarboe, Michelle Carnazza, Raj Tiwari, Xiu-min Li. Re-purposing traditional Chinese anti-asthma formula ASHMI for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1855.

Gut microbial modulation in the treatment of chemotherapy-induced diarrhea with Shenzhu Capsule

BackgroundGut microbiota plays a crucial role in the treatment of gastrointestinal (GI) diseases such as chemotherapy-induced diarrhea (CID). Shenzhu Capsule (SZC) is a Chinese herbal formula, which is composed of Renshen (rhizomes of Panax ginseng C. A. Mey.) and Baizhu (rhizomes of Atractylodes macrocephala Koidz.). Many Chinese traditional anti-diarrheal formulae that contain Renshen and Baizhu are capable of effectively alleviating CID. However, the efficacy in vivo and potential mechanism of SZC (the form of compatibility of Renshen and Baizhu) in the treatment of CID had not been elucidated. Here, this study aimed to investigate whether SZC exhibited the anti-diarrheal activity, and whether gut microbiota was involved in the therapeutic effect of SZC on CID.MethodsHigh performance liquid chromatography (HPLC), gas chromatography-mass spectrometer (GC-MS) and infrared spectroscopy (IR) analyses were used to characterize the extracted components in SZC. The mice were orally administrated with SZC in a preventive mode on the first 2 days of this experiment, and then intraperitoneally injected with 5-FU (40 mg/kg/d) for 6 days. SZC treatment lasted until the 3rd day after the end of 5-FU chemotherapy. We investigated the effects of SZC on body weights, diarrhea, thymus/spleen indexes, colonic tissues, and gut microbiota. Colonic histology was examined by hematoxylin-eosin (HE) staining. 16S rDNA Amplicon Sequencing was used to analyze the gut microbial structure from fecal samples.ResultsSZC significantly increased the body weights and thymus/spleen indexes, alleviated diarrhea, and reversed histopathological changes of colons. In addition, gut microbiota analysis revealed that the overall structure of gut microbiota in CID mice was disturbed, but reversed to the normal state after SZC treatment. At genus level, SZC significantly inhibited the growth of some potential pathogens associated with diarrhea, such as Clostridiumm, Bacteroides, Parabacteroides, Alloprevotella, Acinetobacter and Pseudomonas.ConclusionsIn our study, these data illustrated that SZC inhibited the growth of many potential pathogens during the alleviation of CID. Gut microbial modulation was associated with the anti-diarrheal activity of SZC.

Modulation of transporter activity of OATP1B1 and OATP1B3 by the major active components of Radix Ophiopogonis

Radix Ophiopogonis is often an integral part of many traditional Chinese formulas, such as Shenmai injection used to treat cardio-cerebrovascular diseases. This study aimed to investigate the influence of the four active components of Radix Ophiopogonis on the transport activity of OATP1B1 and OATP1B3.The uptake of rosuvastatin in OATP1B1-HEK293T cells were stimulated by methylophiopogonanone A (MA) and ophiopogonin D′ (OPD′) with EC50 calculated to be 11.33 ± 2.78 and 4.62 ± 0.64 μM, respectively. However, there were no remarkable influences on rosuvastatin uptake in the presence of methylophiopogonanone B (MB) or ophiopogonin D (OPD). The uptake of atorvastatin in OATP1B1-HEK293T cells can be increased by MA, MB, OPD and OPD′ with EC50 calculated to be 6.00 ± 1.60, 13.64 ± 4.07, 10.41 ± 1.28 and 3.68 ± 0.85 μM, respectively.The uptake of rosuvastatin in OATP1B3-HEK293T cells was scarcely influenced by MA, MB and OPD, but was considerably increased by OPD′ with an EC50 of 14.95 ± 1.62 μM. However, the uptake of telmisartan in OATP1B3-HEK293T cells was notably reduced by OPD′ with an IC50 of 4.44 ± 1.10 μM, and barely affected by MA, MB and OPD.The four active components of Radix Ophiopogonis affect the transporting activitives of OATP1B1 and OATP1B3 in a substrate-dependent manner.

RRR-α-tocopherol as a Predominant Stereo-isomer in Chinese Breast Milk During Lactation Stages (P11-057-19)

ObjectivesHuman milk is the most important source for neonates to acquire adequate vitamin E for their immune system and brain growth. Among all tocopherols, infant brain discriminates in favor of the natural occurring RRR-α-tocopherol against the synthetic α-tocopherol stereoisomers and other tocopherols. However, the stereoisomer profiles of α-tocopherol in Chinese human milk have not been previously reported. This study aimed to analyze the stereoisomer profile of α-tocopherol in Chinese human milk over different lactation stages. MethodsColostrum (day 0–7), transitional milk (day 8–15) and mature milk (day 40–45) were collected longitudinally from 89 healthy lactating mothers of full-term, singleton delivery. The levels of α-tocopherol stereoisomers (RRR, RSR, RSS, RRS, Σ2S) were determined by high performance liquid chromatography with fluorescence detection. ResultsIn three lactation stages, RRR-α-tocopherol is the predominated stereoisomers in Chinese human milk (P < 0.0001), accounting for an average proportion of 85% of total α-tocopherol. In contrast, the ratios of the synthetic stereoisomers were RRS, 5.10-6.02%; RSR, 2.32-3.31%, RSS, 2.66-2.85%; and Σ2S, 2.89%-3.49%. The mean total α-tocopherol was 9.20mg/L in colostrum but sharply declined to 4.10 mg/L in mature milk. After taking the different breastfeeding volumes over lactation stages into consideration, Chinese human milk constantly provided about 3.5 mg/day α-tocopherol and 2.98 mg/day RRR-α-tocopherol to infants. ConclusionsRRR-α-tocopherol is the predominated stereoisomer in Chinese human milk over different lactation stages. Chinese breastmilk supply higher % of RRR- stereoisomer as 85% of total α-tocopherol than US report as 75%. There is, therefore, a demand to add matched level of RRR- α-tocopherol in Chinese formula. Funding SourcesAbbott.

RAM study on general standard of maximum residue limits for pollution-free traditional Chinese medicine based on Chinese Pharmacopoeia formula

The excessive pesticide residues and heavy metals in traditional Chinese medicine seriously endanger human health and the sustainable development of Chinese medicine industry. In order to improve the quality of traditional Chinese medicine and establish a general standard for maximum residue limits(MRL) of pesticides in pollution-free traditional Chinese medicine and decoction pieces, and to ensure the safety of clinical medication from its origin, MRLs were calculated based on the formula(MRL=A×W/100M) from Chinese Pharmacopeia, comparing it with the current Chinese and international standards as well as literature review, the RAND/UCLA appropriateness method(RAM) was applied to determine the categories and MRLs of pesticides in pollution-free traditional Chinese medicine and decoction pieces. Two questionnaires were drafted for expert panel and appropriateness analysis was carried out with the 9-point Likert scale to determine the general standard for MRLs of pollution-free traditional Chinese medicine and decoction pieces. The results showed that a total of nine experts from different fields scored the necessity of standard-setting and 206 pesticide residue limits respectively. The appropriateness scores of 206 pesticides were greater than 7, and appropriateness rate was 100%, which signifies that the expert panel has reached consensus. In summary, based on the RAM, the general standard for maximum residue limits of pesticides in pollution-free Chinese medicines and decoction pieces has reached an expert consensus. Comparing with the MRLs of medicinal plants and plant-sourced food from CAC, Europe Union, the United States, South Korea, Japan, Australia, New Zealand and Canada, 206 MRLs from this general standard share 88.8% in common, 4.4% of which is higher and 6.8% lower than those international standards. This has provided a basis for standardizing the use of pesticides in pollution-free traditional Chinese medicine.