Radix Saposhnikoviae Research Articles

Chikusetsusaponin IVa Protects against H9N2 Avian Influenza Virus Infection by Inhibiting Inflammation and TLR4/NF-κB Signaling Pathways in vitro and in vivo

Background The prevalence of Hemagglutinin 9 Neuraminidase 2 (H9N2) avian influenza virus (AIV) in poultry in Asia has raised serious concerns about its zoonotic transmission and the potential for a pandemic, underscoring the need for effective therapeutics. Chikusetsusaponin IVa (CHS), a bioactive triterpenoid saponin from Radix saposhnikoviae, has exhibited anti-inflammatory activity in preclinical studies. We hypothesized that CHS could mitigate immunopathology during tumor necrosis factor (TNF)-infection by suppressing excessive inflammation. Objectives CHS is a natural saponin with anti-inflammatory activity. This research aimed to explore the in vitro and in vivo protective effects and mechanisms of CHS against H9N2 AIV infection. Materials and Methods We employed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis for the prediction of the underlying mechanisms, followed by a network analysis approach. In animal experiments, the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathways and associated proteins were assessed using immunohistochemistry and western blot analysis. Results In A549 cells, CHS treatment reduced H9N2 AIV-induced apoptosis in a dose-dependent manner. CHS was found to have a suppressive effect on the mRNA expression of various inflammatory cytokines (including TNF-α, interleukin (IL)-6, IL-1β, and IL-8) as well as mediators such as inducible nitric oxide synthase (iNOS) and prostaglandin-endoperoxide synthase 2 (PTGS2). It can be seen that CHS does have anti-inflammatory effects. Bioinformatics analysis indicated that CHS might exhibit anti-inflammatory effects by modulating cytokine–cytokine receptor interaction and the NF-κB signaling pathways. Building upon this, it was found that CHS blocked the activation of TLR4 and NF-κB signaling pathways in A549 cells infected with H9N2 AIV. In vivo, CHS prolonged the survival time and increased the survival rate of H9N2 AIV-infected mice. CHS was found to have a protective effect on the lungs of infected mice, resulting in reduced damage and lower levels of viral load and inflammation. CHS inhibited the production of proinflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8) and inhibited the activation of TLR4 and NF-κB signaling pathways in the pulmonary tissues of mice that were infected. Conclusion CHS exerts protective effects against H9N2 AIV infection in vitro and in vivo. The anti-inflammatory mechanisms may involve the inhibition of cytokine production and the blockade of TLR4 and NF-κB signaling pathways.

Progress in the Treatment of Allergic Diseases with Radix Saposhnikoviae

Progress in the Treatment of Allergic Diseases with Radix Saposhnikoviae

Radix Saposhnikoviae enhancing Huangqi Chifeng Decoction improves lipid metabolism in AS mice

Ethnopharmacological relevanceHuangqi Chifeng decoction (HQCF) combined with parsnips is a classic Chinese traditional medicine formula that has certain advantages in the clinical treatment of cardiovascular and cerebrovascular diseases. At present, there is an absence of research on the regulatory effect and mechanism of this formula on atherosclerosis (AS). The synergistic effect of Radix Saposhnikoviae (RS) in HQCF is also unclear. Aim of the studyThis study was designed to investigate the role of RS, which is designed as a guide drug for HQCF, in improving the lipid metabolism of AS. Materials and methodsIn this study, we studied the effect of HQCF on ApoE−/− mice before and after RS compatibility. Hematoxylin and eosin (HE) staining and oil red staining were used to evaluate atherosclerotic lesions and lipid accumulation in the aorta and liver, respectively. The expression of adenosine monophosphate-activated protein kinase (AMPK) and pAMPK in the aorta was measured by immunofluorescence, and AMPK and sterol regulatory element binding protein-1 (SREBP-1),fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in liver tissue were measured by Western blot analysis. Metabolomics was used to compare the changes in serum and liver metabolites of ApoE−/− mice before and after RS combination. ResultsCompared with the control group, the serum lipid levels of ApoE−/− mice increased, the aortic intima thickened with plaque formation, and liver tissue pathological changes and lipid deposition occurred. Both (HQCFT without RS)HQCS and HQCF can improve the pathological condition of tissue and regulate the blood lipid level. It was noted that HQCF could promote the phosphorylation of AMPK to activate it, inhibit the expression of SREBP-1c and FAS, reduce lipid synthesis, and inhibit ACC to promote the oxidative decomposition of fatty acids. Serum and liver metabolome results showed that HQCS and HQCF treated AS mainly by regulating glycerophospholipid metabolism, sphingolipid metabolism and the arachidonic acid metabolism pathway. Importantly, HQCF showed better efficacy in regulating lipid metabolism than the HQCS group. ConclusionHQCF decoction reduces atherosclerotic lesions in the aorta and lipid accumulation in the liver, which may regulate lipid transport and metabolic function by activating the AMPK pathway. These effects can be attributed to the guidance and synergism of RS.

Sodium nitroprusside improved the quality of Radix Saposhnikoviae through constructed physiological response under ecological stress

The ecological significance of secondary metabolites is to improve the adaptive ability of plants. Secondary metabolites, usually medicinal ingredients, are triggered by unsuitable environment, thus the quality of medicinal materials under adversity being better. The quality of the cultivated was heavily declined due to its good conditions. Radix Saposhnikoviae, the dried root of Saposhnikovia divaricata (Turcz.) Schischk., is one of the most common botanicals in Asian countries, now basically comes from cultivation, resulting in the market price being only 1/10 to 1/3 of its wild counterpart, so improving the quality of cultivated Radix Saposhnikoviae is of urgency. Nitric oxide (NO) plays a crucial role in generating reactive oxygen species and modifying the secondary metabolism of plants. This study aims to enhance the quality of cultivated Radix Saposhnikoviae by supplementing exogenous NO. To achieve this, sodium nitroprusside (SNP) was utilized as an NO provider and applied to fresh roots of S. divaricata at concentrations of 0.03, 0.1, 0.5, and 1.0 mmol/L. This study measured parameters including the activities of antioxidant enzymes, secondary metabolite synthesis enzymes such as phenylalanine ammonia-lyase (PAL), 1-aminocyclopropane-1-carboxylic acid (ACC), and chalcone synthase (CHS), as well as the contents of NO, superoxide radicals (O2·−), hydrogen peroxide (H2O2), malondialdehyde (MDA), and four secondary metabolites. The quality of Radix Saposhnikoviae was evaluated with antipyretic, analgesic, anti-inflammatory effects, and inflammatory factors. As a result, the NO contents in the fresh roots were significantly increased under SNP, which led to a significant increase of O2·−, H2O2, and MDA. The activities of important antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were found to increase as well, with their peak levels observed on the 2nd and 3rd days. PAL, ACC, and CHS activities were also significantly enhanced, resulting in the increased secondary metabolite contents of Radix saposhnikoviae in all groups, especially the 0.5 mmol/L SNP. The four active ingredients, prim-O-glucosylcimifugin, cimifugin, 4′-O-β-d-glucosyl-5-O-methylvisamminol, and sec-O-glucosylhamaudol, increased by 88.3%,325.0%, 55.4%, and 283.8%, respectively, on the 3rd day. The pharmaceutical effects of Radix Saposhnikoviae under 0.5 mmol/L SNP were significantly enhanced. Exogenous SNP can induce the physiological response of S. divaricata under adverse conditions and significantly improve the quality of Radix Saposhnikoviae.

Alcohol Extract of YFXJ Decoction Reverses the Drug Resistance of Human Lung Adenocarcinoma Cell Line A549/DDP.

Objective Lung cancer is the wide and common tumor. This study was designed to explore the effect of YFXJ formula on non-small-cell lung cancer (NSCLC) cell lines. Methods YFXJ formula (mainly composed of Astragalus membranaceus, Atractylodes macrocephala, Radix Saposhnikoviae, Radix Glehniae, coix seed, Herba Sabina chinensis, Hedyotis diffusa, Pericarpium Citri Reticulatae, sarcophagus martensii, Prunella vulgaris, Meretrix meretrix, and oyster) was extracted with 75% ethanol. We performed MTT, FACS, TUNEL, and mass spectrometry to study the effect of YFXJ formula on A549/DDP cells. Results The results showed that YFXJ could inhibit the growth of A549/DDP cells, and it can reverse the sensitivity of A549/DDP cells to cisplatin. YFXJ inhibits the expression of MDR1, MRP1, and LRP genes in A549/DDP cells. Conclusion YFXJ formula can reverse the drug resistance of A549/DDP cell, which could be through activation of autophagy.

Chinese herbal formula Tongxie Yaofang for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized, multiple-blind, placebo-controlled trial

IntroductionDiarrhea-predominant irritable bowel syndrome (IBS-D) is a bowel disease with a high incidence. It significantly reduces the quality of life of patients and affects the patient's daily activities and mental health. No specific therapeutic medications for IBS-D have been found. Published clinical trials suggest that Chinese herbal formula Tongxie Yaofang (TXYF) for IBS-D may be effective. However, high-quality clinical evidence supporting its use in IBS-D is still lacking. This trial aims to evaluate the therapeutic effects and safety of TXYF for IBS-D in adults.Methods/designA randomized, multiple-blind, placebo-controlled trial will be conducted. It will consist of an 8-week intervention followed by a 3-month follow-up period.The target sample size is 96 IBS-D patients aged 18 to 65 years. The eligible participants will be randomly allocated to either TXYF or placebo group in a ratio of 1:1. Participants in the experimental group will take TXYF granules, while participants in the control group will be given TXYF placebo granules. The primary outcome will be the degree of IBS symptom severity measured using the scale of IBS symptom severity score. The secondary outcomes include: (a) stool frequency, and (b) stool consistency measured using the Bristol stool scale, (c) quality of life measured using the scale of IBS-quality of life, (d) anxiety measured using the self-rating anxiety scale, (e) depression measured by the self-rating depression scale, and (f) the safety of using TXYF and placebo. Safety monitoring and assessment will be undertaken throughout treatment.DiscussionChinese herbal formula TXYF consists of four Chinese herbs: Atractylodes macrocephala Koidz., Paeonia lactiflora Pall., Citrus × aurantium L., and Radix saposhnikoviae. It has been used for diarrhea for hundreds of years and may have a potential benefit in treating adults with IBS-D, but due to lack of high-quality evidence, we designed a randomized, multiple-blind, placebo-controlled trial to evaluate its therapeutic effects and safety. This trial will provide important data to guide the clinical practice of TXYF for the treatment of IBS-D in adults.Trial registrationISRCTN registry ISRCTN12453166. Registered on 23 March 2021.

Medication Rule Analysis of the Diagnosis and Treatment Programs of Chinese Medicine for the Prevention and Treatment of COVID-19 in China.

ObjectivesTo summarize the measures and rules of Chinese medicine (CM) and provide reference for clinical application in the prevention and treatment of coronavirus disease (COVID-19).MethodsThe data source was from CM COVID-19 prevention and treatment programs on government websites and official media websites of the different provinces and cities. The search lasted from December 8, 2019 to March 10, 2020. Main variables were medication frequency and combinations of medicines. Cluster analysis and complex network analysis were used by prevention and treatment stage and by area.ResultsAmong 27 CM diagnosis and treatment plans, 203 therapeutic prescriptions were enrolled, of which the top 4 herbs were: Radix glycyrrhizae, Semen armeniacae amarum, Herba ephedrae, and Herba agastachis, respectively. The core combinations were Herba ephedrae and Semen armeniacae amarum. Forty-eight preventive formulae were identified. Ten herbs, including Radix Astragali seu hedysari, Radix glycyrrhizae, Radix saposhnikoviae, Flos lonicerae, etc. were most frequently used. The core prescription of CM compatibility was Radix astragali seu hedysari, Radix glycyrrhizae, and Radix saposhnikoviae, which is the main component of Yu Ping Feng San. There were 45 prevention and treatment prescriptions in East China; the most used CM was Radix glycyrrhizae, Herba agastachis, Pericarpium citri reticulatae, and Gypsum fibrosum. Fifty prescriptions were identified in North China. According to CM analyses, Herba agastachis, Semen armeniacae amarum, Herba ephedrae, and Poria were most frequently used.ConclusionsCM for COVID-19 prevention mainly focuses on improving human immunity; for treatment, prescription focuses on clearing the lungs and removing dampness. Prescriptions vary with regions, perhaps due to climatic and environmental differences, which help clinicians to quickly make CM plans and treat patients according to clinical status, further minimizing resource wastage.Electronic Supplementary MaterialSupplementary materials (Appendices) are available in the online version of this article at 10.1007/s11655-021-2880-1

Panaxynol induces fibroblast-like synovial cell apoptosis, inhibits proliferation and invasion through TLR4/NF-κB pathway to alleviate rheumatoid arthritis

Background and purposePanaxynol (PAL, PubChem CID: 5281149) is a common natural minor component in Umbelliferae plants, such as Radix Saposhnikoviae Divaricatae. Modern pharmacology studies show that PAL has nutritional value and anti-inflammatory and other pharmaceutical activities. Therefore, the scientific hypothesis of PAL in the treatment of rheumatoid arthritis was put forward, and the hypothesis was further verified by Fibroblast-like synovial cells (RA-FLS) and Collagen Induced Arthritis (CIA) rats models. Experimental methodCIA method was used to establish a rat arthritis model. After extracting RA-FLS, flow cytometry and immunofluorescence were used to explore the effect of PAL on the apoptosis and proliferation of RA-FLS. Wound healing and transwell experiment explored the effect of PAL on the migration and invasion of RA-FLS. Western blot analysis explored the inner mechanism of the effect of PAL on RA-FLS. At the same time, it also explored the role of PAL in CIA rats, including pathological section detection and western blot analysis. Main resultsPAL can promote the apoptosis and inhibit the proliferation, migration and invasion of RA-FLS. PAL can also reduce joint swelling in CIA rats, reduce pannus formation and inflammatory infiltration in the joints. Western blot analysis showed that PAL mainly played a role through the TLR4/NF-κB signaling pathway. ConclusionThe results of in vivo and in vitro experiments show that PAL can effectively alleviate the condition of RA, and may be a potential drug for the treatment of RA.

An integrated strategy for the identification and screening of anti-allergy components from natural products based on calcium fluctuations and cell extraction coupled with HPLC-Q-TOF-MS.

Allergic diseases are a significant public health problem worldwide. Traditional Chinese medicines (TCMs) with reported anti-allergy effects may be important sources for the development of new anti-allergy drugs. Thus, establishing an analytical method that can simultaneously identify and screen anti-allergic compounds in TCMs is important. The increased concentrations of intracellular calcium ions resulting in mast cell degranulation releasing active mediators play a key role in allergic diseases, which can be used as a potential index to identify anti-allergic herbs and compounds. In this study, we provide a new strategy that was applied to screening natural anti-allergic compounds based on fluorescence calcium ion (Ca2+) fluctuation integrated with cell extract and high-performance liquid chromatography-mass spectrometry (HPLC-MS). A low-cost, convenient fluorescence detection Ca2+ signaling method was established and successfully applied to identify three herbs. Then, the method was integrated with biospecific cell fishing and HPLC-MS to screen potential active components that have the effect of stabilizing the cell membrane of rat basophilic leukemia granulocytes (RBL-2H3). Seven components, namely, albiflorin and paeoniflorin from Radix Paeoniae Alba, ononin and formononetin from Radix Astragali, cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol, and prim-O-glucosylcimifugin from Radix Saposhnikoviae were fished. These seven compounds have the effect of inhibiting cell Ca2+ influx. 4'-O-β-D-Glucosyl-5-O-methylvisamminol, prim-O-glucosylcimifugin, paeoniflorin, ononin, and formononetin significantly inhibit the release of β-hexosaminidase, which is equivalent to the positive drug. In conclusion, the integrated strategy of fluorescence detection calcium ion kinetic method binding with biospecific cell fishing was an effective mode to identify and screen natural anti-allergic compounds.

The protective effect of 5-O-methylvisammioside on LPS-induced depression in mice by inhibiting the over activation of BV-2 microglia through Nf-κB/IκB-α pathway

Background5-O-methylvisammioside (MeV), also known as 4′-O-β-D-glucosyl-5-O-methylvisamminol, is a conventional marker compound for quality control of roots of Saposhnikovia diviaricata (Radix Saposhnikoviae), which exhibits anti-inflammatory and neuroprotective activities. PurposeAccording to the activity of MeV, we speculated that MeV may have antidepressant effect on LPS induced depression, and further explored its mechanism. Study DesignFirst, to explore the effect and mechanism of MeV on LPS-induced depression in mice, and then to further explore the effect and mechanism of MeV on LPS-activated BV-2 microglia. MethodsBy the OFT, EPM, TST and FST behavioral tests, to explore the effect of MeV pretreatment on the behavior of LPS-induced depression mice. ELISA and Griess method were used to detect the changes of the serum TNF-α and IL-6 levels, the hippocampus SOD and MDA levels, and the NO, SOD, MDA, TNF-α and IL-6 levels in the culture medium of LPS-stimulated BV-2 microglia. Western blot was used to analyze the protein expression in the Nf-κB/IκB-α and BDNF/TrkB pathway in the hippocampus of mice and BV-2 microglia. ResultsMeV (4 mg/kg, i.p.) pretreatment significantly improves the activity and exploration ability of LPS-induced depression mice, and reduces the immobility time. MeV inhibited the production of pro-inflammatory cytokines in the serum of mice induced by LPS, such as IL-6 and TNF-α. MeV also increased the levels of SOD and reduces the expression of MDA in the hippocampus, thus promoting the alleviation of depressive symptoms in mice. Western blotting analysis showed that the antidepressant activity of MeV was related to the decrease of Nf-κB nuclear transport, the inhibition of IκB-α phosphorylation, and the increase of BDNF and TrkB expression. MeV (40 μM) significantly reduced the contents of NO, MDA, TNF-α and IL-6 in the culture medium of LPS-stimulated BV-2 microglia, and increased the content of SOD. ConclusionMeV can regulate the neurotrophic factors in the mouse brain, reduce the content of inflammatory factors by the Nf-κB/IκB-α pathway, improve oxidative stress, and inhibit the excessive activation of LPS-stimulated BV -2 microglia. It effectively reversed the depression-like behAavior induced by LPS in mice.

Development of a method to screen and isolate lipoxidase inhibitors from Radix Saposhnikoviae via ultrafiltration liquid chromatography combined with metablism in vitro.

Radix Saposhnikoviae is an excellent source of chromones, the consumption of which has been shown to positively affect human health, such as anti-inflammatory and antioxidant activities in vivo, and it also has been used to treat headache, inflammation, and cancer as a herbal medicine or functional soup. Isolation and screening of lipoxidase (LOX) inhibitors from Radix Saposhnikoviae. As a result, the metabolism of the active ingredients in cytochrome P450 (CYP450) in vitro was identified. Screen and identify the LOX inhibitors from Radix Saposhnikoviae by ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS). Then take the isolation and purification of the inhibitors by high-speed counter-current chromatography (HSCCC) and semi-preparative high-performance liquid chromatography (HPLC). Furthermore, the active ingredients were used to study the metabolism in vitro in CYP450. Subsequently, the specific binding ligands, prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminol (with purities of 95.28, 92.33%, and 97.89, respectively) were separated by HSCCC. Semi-preparative HPLC was applied to separate the four major compounds in Radix Saposhnikoviae and identify them as prim-O-glucosylcimifugin, 5-O-methylvisamminol, sec-O-glucosylhamaudol, and hamaudol, which were obtained with relatively high purity. Furthermore, the three chromone possible metabolism pathways were obtained. The results demonstrated that UF-LC-MS combined with HSCCC and semi-preparative HPLC is not only a powerful tool for screening and isolating LOX inhibitors in complex samples, but also a useful platform for discovering bioactive compounds for anti-inflammatory activity. This study provides information regarding the active ingredients of chromones in Radix Saposhnikoviae and a framework for anti-inflammatory activity treatment.

Therapeutic effect of herb-separated moxibustion at Jinsuo (GV 8)-eight-diagram points on diarrhea-type irritable bowel syndrome of liver stagnation and spleen deficiency

To observe the clinical therapeutic effect of herb-separated moxibustion at Jinsuo (GV 8)- eight-diagram points on diarrhea-type irritable bowel syndrome (IBS-D) of liver stagnation and spleen deficiency as compared with oral administration of pinaverium bromide tablets and Chinese herbal decoction, tongxieyaofang. A total of 126 patients with IBS-D of liver stagnation and spleen deficiency were randomized into a herb-separated moxibustion group (moxibustion group), a western medication group and a Chinese herbal medication group, 42 cases in each one. In the moxibustion group, the herb-separated moxibustion was applied to Jinsuo (GV 8)-eight-diagram points. The herbs in tongxieyaofang (fried rhizoma atractylodis macrocephalae, fried radix paeoniae alba, pericarpium citri reticulatae and radix saposhnikoviae) were ground into herbal paste and the paste was put on Jinsuo (GV 8)-eight-diagram points. The suspending moxibustion was exerted over the points for 40 min, once daily. In the western medication group, pinaverium bromide tablets were taken orally, 50 mg each time, three times a day. In the Chinese herbal medication group, the decoction of tongxieyaofang was taken orally, one dose a day, taking separately in two times. The duration of treatment was 8 weeks in each group. Before and after treatment, the symptom score of traditional Chinese medicine (TCM), gastrointestinal (GI) symptom score, the score of IBS symptom severity scale (IBS-SSS) and the score of IBS quality of life (IBS-QOL) scale were observed in patients of each group separately. The clinical therapeutic effect was evaluated. After treatment, the scores of TCM symptoms, GI symptom scores and IBS-SSS scores were all obviously reduced in each group (P<0.05). Each of the scores in the moxibustion group was lower than the western medication group and the Chinese herbal medication group respectively (P<0.05). After treatment, the scores of each of eight subscale structures of IBS-QOL scale, named dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual intercourse and relationship, were all increased obviously in each group (P<0.05). The scores of each of eight subscale structures in the moxibustion group were higher than the western medication group and the Chinese herbal medication group respectively (P<0.05). The total effective rate was 92.9% (39/42) in the moxibustion group, higher than 71.4% (30/42) in the western medication group and 73.8% (31/42) in the Chinese herbal medication group respectively (P<0.05). Herb-separated moxibustion at Jinsuo (GV 8)-eight-diagram points remarkably relieves gastrointestinal symptoms and improves the quality of life in patients of diarrhea-type irritable bowel syndrome of liver stagnation and spleen deficiency, and its clinical therapeutic effect is superior to oral administration of either pinaverium bromide tablets or tongxieyaofang.

Saposhnikovia divaricata-An Ethnopharmacological, Phytochemical and Pharmacological Review.

Saposhnikovia divaricata (Turcz.) Schischk., a perennial herb belonging to the family Umbelliferae, is widely distributed in Northeast Asia. Its dried root (Radix Saposhnikoviae) is used as a Chinese herbal medicine for the treatment of immune system, nervous system, and respiratory diseases. Phytochemical and pharmacological studies have shown that the main constituents of S. divaricata are chromones, coumarins, acid esters, and polyacetylenes, and these compounds exhibited significant anti-inflammatory, analgesic, antioxidant, antiproliferative, antitumor, and immunoregulatory activities. The purpose of this review is to provide comprehensive information on the botanical characterization and distribution, traditional use and ethnopharmacology, phytochemistry, and pharmacology of S. divaricata for further study concerning its mechanism of action and development of better therapeutic agents and health products from S. divaricata.Electronic Supplementary MaterialSupplementary material (Appendixes 1–10) is available in the online version of this article at 10.1007/s11655-020-3091-x.

Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs.

ObjectiveSince December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies.MethodsHistorical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases.ResultsThe use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi’s Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24–0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao).ConclusionsBased on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM.Electronic Supplementary MaterialSupplementary material is available in the online version of this article at 10.1007/s11655-020-3192-6.

Quality evaluation of heat stress treated Radix saposhnikoviae using pharmacokinetic and pharmacologic methods

Quality evaluation of heat stress treated Radix saposhnikoviae using pharmacokinetic and pharmacologic methods

Houshiheisan and its components promote axon regeneration after ischemic brain injury.

Houshiheisan, a classic prescription in traditional Chinese medicine, contains Flos Chrysanthemi, Radix Saposhnikoviae, Ramulus Cinnamomi, Rhizoma Chuanxiong, Radix et Rhizoma Asari, Radix Platycodonis, Rhizoma Atractylodis macrocephalae, Poria, Rhizoma Zingiberis, Radix Angelicae sinensis, Radix et Rhizoma Ginseng, Radix Scutellariae and Concha Ostreae. According to traditional Chinese medicine theory, Flos Chrysanthemi, Radix Saposhnikoviae, Ramulus Cinnamomi, Rhizoma Chuanxiong, Radix et Rhizoma Asari and Radix Platycodonis are wind-dispelling drugs; Rhizoma Atractylodis macrocephalae, Poria, Rhizoma Zingiberis, Radix Angelicae sinensis and Radix et Rhizoma Ginseng are deficiency-nourishing drugs. A large number of randomized controlled trials have shown that Houshiheisan is effective in treating stroke, but its mechanism of action is unknown. Axonal remodeling is an important mechanism in neural protection and regeneration. Therefore, this study explored the effect and mechanism of action of Houshiheisan on the repair of axons after cerebral ischemia. Rat models of focal cerebral ischemia were established by ligating the right middle cerebral artery. At 6 hours after model establishment, rats were intragastrically administered 10.5 g/kg Houshiheisan or 7.7 g/kg wind-dispelling drug or 2.59 g/kg deficiency-nourishing drug. These medicines were intragastrically administered as above every 24 hours for 7 consecutive days. Houshiheisan, and its wind-dispelling and deficiency-nourishing components reduced the neurological deficit score and ameliorated axon and neuron lesions after cerebral ischemia. Furthermore, Houshiheisan, and its wind-dispelling and deficiency-nourishing components decreased the expression of proteins that inhibit axonal remodeling: amyloid precursor protein, neurite outgrowth inhibitor protein A (Nogo-A), Rho family small GTPase A (RhoA) and Rho-associated kinase 2 (Rock2), and increased the expression of growth associated protein-43, microtubule-associated protein-2, netrin-1, Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42). The effect of Houshiheisan was stronger than wind-dispelling drugs or deficiency-nourishing drugs alone. In conclusion, Houshiheisan, and wind-dispelling and deficiency-nourishing drugs promote the repair of axons and nerve regeneration after cerebral ischemia through Nogo-A/RhoA/Rock2 and Netrin-1/Rac1/Cdc42 signaling pathways. These effects are strongest with Houshiheisan.

Application of ionic liquid-based ultrasonic-assisted extraction followed by rapid resolution LC-ESI/MS to chromone analysis from radix saposhnikoviae

Ionic liquid-based ultrasonic-assisted extraction (ILUAE) was successfully applied to the extraction of the four chromones (prim-O-glucosylcimifugin, cimifugin, 5-O-methylvisammioside, and sec-O-glucosylhamaudol) from Saposhnikovia divaricata (Radix Saposhnikoviae) for the first time. A series of l-alkyl-3-methylimidazolium ILs differing in anion and cation compositions was evaluated for extraction efficiency, and [C3MIM]Br was selected as the optimal solvent. In addition, ultrasound extraction parameters were optimized, and the chromones were directly quantified and analyzed by rapid resolution liquid chromatography-electrospray ionization/mass spectrometry (RRLC-ESI/MS). The optimal conditions were as follows: 0.4 M concentration of [C3MIM]Br, 20:1 solvent to solid ratio, and ultrasonic time, temperature, and frequency of 5 min, 40 °C, and 50 kHz, respectively. This approach obtained the highest extraction yield of 10.188 ± 0.473 mg g−1 for total chromones. Compared with regular UAE, the proposed approach exhibited a higher efficiency (61.56% increase) and shorter extraction time (nine times shorter). Also, ILUAE was an efficient, rapid, and simple sample preparation technique for extraction of chromones, and the established RRLC-DAD method could serve as a rapid and effective technique for extracting chromones from Radix Saposhnikoviae.

Metabolic profiling of the traditional Chinese medicine formulation Yu Ping Feng San for the identification of constituents relevant for effects on expression of TNF-α, IFN-γ, IL-1β and IL-4 in U937 cells

Yu Ping Feng San (YPFS) is a classical TCM formulation which has been traditionally used for treatment of immune system related diseases such as chronic bronchitis, allergic rhinitis and asthma. The formula is a mixture of Radix Saposhnikoviae (Fangfeng), Radix Astragali (Huangqi), and Rhizoma Atractylodis macrocephalae (Baizhu). TLC- and LC-DAD-ESI-MS/MS methods have been developed for the analysis of the metabolic profiles of the single herbs and of the formula. Decoctions and ASE extracts were analyzed in order to trace components of the individual herbs in YPFS. Nine constituents of Radix Saposhnikoviae, ten constituents of Radix Astragali and five constituents of Rhizoma Atractylodis macrocephalae have been assigned in the chemical profiles of the formula, which now allow the standardisation of YPFS. The pharmacological testing showed that all extracts significantly inhibited expression of TNF-α, IFN-γ, and IL-1β in U937 cells, while the inhibition of IL-4 was consistently low. Compared to conventional analyses which are focused on a limited set of compounds, metabolomics approaches, together with novel data processing tools, enable a more holistic comparison of the herbal extracts. In order to identify the constituents which are relevant for the immunomodulatory effects of the formula, metabolomics studies (PCA, OPLS-DA) have been performed using UPLC/QTOF MS data.

Effect of Chinese herbal medicine treatment on plasma lipid profile and hepatic lipid metabolism in Hetian broiler

The purpose of this study was to investigate whether adding a Chinese herbal hedicine (CHM, including astragalus membranaceus, codonopsis pilosula, poria cocos, bighead atractylodes rhizome, fructus crataegi, folium epimedii, radix saposhnikoviae, and pericarpium citri reticulatae) diet has effects on lipid metabolism in the liver of the broiler. Six-hundred-thirty Hetian broilers were divided into 3 groups including base diet (control), 0.3%, or 1% CHM diets, for 130 days. The results showed that CHM treatment significantly increased the slaughter performance. CHM treatment decreased plasma triglyceride (TG) and nonesterified fatty acid (NEFA) concentrations; up-regulated the expression of peroxisome proliferator activated receptor (PPAR), the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) and its downstream proteins involved in NEFA oxidation including carnitine palmitoyltransferase-1, liver fatty acid binding protein, and PPARα; and it significantly decreased fatty acid synthetase, stearoyl-CoA desaturase, acyl-CoA synthetase long-chain family member 1 and acetyl-CoA carboxylase expression to inhibit NEFA synthesis. In addition, the CHM treatment increased plasma insulin (INS) levels and up-regulated insulin receptors (INSR) glycerol-3-phosphate acyltransferase and mitochondrial and 1-acylglycerol-3-phosphate O-acyltransferase 6 mRNA expression to enhance TG synthesis. The protein levels of phosphatidylinositol 3-hydroxy kinase (PI3K), serine/threonine protein kinase (Akt), S6 kinase (S6K), phospho-serine/threonine protein kinase (p-Akt), and phospho-S6 kinase (p-S6K) also were increased. PI3K, p-Akt, and p-S6K were significantly up-regulated in the liver. These data suggest that the CHM may be a beneficial compound to decrease plasma NEFA and TG levels by activating the INS/INSR-PI3K-Akt-SREBP1c pathway resulting in fat content reduction in the carcass.

Prim-O-glucosylcimifugin Attenuates Lipopolysaccharideinduced Inflammatory Response in RAW 264.7 Macrophages.

Background:Radix Saposhnikoviae (RS) exerts anti-inflammatory, analgesic, antipyretic, antioxidation effects and has been used in traditional Chinese medicine to treat common colds, headache, and rheumatoid arthritis. Prim-O-glucosylcimifugin (POG) is the highest content chromone and one of the major active constituents in RS.Objective:The study was aimed to explore the anti-inflammation effects of POG in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.Materials and Methods:Cell viability was detected by Cell Counting Kit-8 assay. Production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 was assessed by enzyme-linked immunosorbent assay. Real-time polymerase chain reaction and Western blot were performed to analyze mRNA and protein levels, respectively.Results:During the whole experiment, 15, 50, and 100 μg/mL of POG had no cytotoxicity on RAW 264.7 cells. POG dose-dependently inhibited the production of NO, TNF-α, IL-1β, and IL-6 that were induced by LPS. POG treatment downregulated the mRNA and protein expression inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) in LPS-activated RAW 264.7 macrophages in a concentration-dependent manner. Furthermore, LPS-induced JAK2/STAT3 activation was prevented in RAW 264.7 macrophages by POG treatment. STAT3 overexpression significantly reversed the effects of POG on LPS-activated RAW 264.7 macrophages.Conclusion:These results demonstrate that POG exerts anti-inflammatory effects through the inhibition of iNOS and COX-2 expression by inhibiting the phosphorylation of JAK2/STAT3.SUMMARY POG exerts anti-inflammatory effects in RAW 264.7 macrophages through the inhibition of iNOS and COX-2 expression by inhibiting JAK2/STAT3 signaling. Abbreviations used: LPS: Lipopolyssacharide; NO: Nitric oxide; TNF-α: Tumor necrosis factor-α; IL: Interleukin; RS: Radix Saposhnikoviae; POG: Prim-O-glucosylcimifugin; iNOS: Inducible NO synthase; COX2: Cyclooxygenase; FBS: Fetal bovine serum; DMSO: Dimethylsulfoxide; CCK-8: Cell Counting Kit; RIPA: Radio immunoprecipitation assay buffer; ECL: Enhanced chemiluminescence; SD: Standard deviation; ELISA: Enzyme-Linked immunosorbent assay.