Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing Arginase-1 in rheumatoid arthritis.

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL-17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.

Pharmacokinetic investigation of principal active constituents in renal fibrotic rats after oral administration of crude and salt-processed eucommiae cortex extracts / 药学学报

A quantitative analysis method for six principal active constituents (acubin, geniposidic acid, chlorogenic acid, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside) of crude Eucommiae Cortex (EC) and its salt-processed product extracts was developed to investigate and compare their pharmacokinetic behaviors in adenine-induced renal fibrotic rats in vivo. UHPLC-QqQ-MS/MS technology was employed. Scan was conducted in negative ion mode and quantitative determination was carried out by MRM paired ion. The established method was fully validated by specificity, linearity, precision, accuracy, stability, recovery, and matrix effect, and the results of methodological investigation met the requirements of biological sample analysis. Then, a quick, sensitive, and accurate method was successfully established, which could simultaneously measure the contents of six active constituents of crude and salt-processed EC extracts in rat plasma. After a single administration to renal fibrotic rats of crude EC and its salt-processed product extracts, the plasma concentration of each constituent at different time points was measured, the pharmacokinetic parameters were calculated and the concentration time curves were structured. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that compared to the crude Eucommiae Cortex group, the tmax of aucubin, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside in the salt-processed Eucommiae Cortex group rat plasma were significantly lower than those in the crude group (P < 0.05, P < 0.01); the Cmax and AUC0-48 h of chlorogenic acid, the Cmax, AUC0-48 h and AUC0-∞ of pinoresinol di-O-glucopyranoside, and the Cmax of geniposide and pinoresinol 4-O-glucopyranoside were significantly higher than those in the crude group (P < 0.05, P < 0.01). Our investigation found that compared to crude Eucommiae Cortex, a variety of active ingredients could play a role of quick effect with higher peak blood concentration and bioavailability after oral administration of salt-processed Eucommiae Cortex, which were consistent with the traditional Chinese medicine theory of "salt-processing enhancing drug into kidney meridian", providing an experimental basis for the selection of quality control indexes and the in-depth study of processing mechanisms and metabolic rules in vivo of Eucommiae Cortex and its salt-processed product.

Modified acupuncture therapy, long-term acupoint stimulation versus sham control for weight control: a multicenter, randomized controlled trial.

Objective: Long-term acupoint stimulation (LAS), also called embedding acupuncture, is a modified acupuncture technique. The preliminary results have demonstrated its efficacy in body-weight control. However, the low quality of available trials limited its application. This study aimed to evaluate the efficacy and safety of LAS in body-weight control by using a randomized, parallel, sham-controlled clinical trial design. Methods: This was a randomized, single-blind, sham-controlled clinical trial including 84 adult participants (18-60 years) with a body mass index (BMI) of ≥ 24 kg/m2 conducted in three general hospitals in Shanghai, China. Participants were equally assigned to receive LAS or sham LAS (SLAS) once per 10 days, eight times in total. After completion, an additional intervention with a 3-month follow-up period was set to examine the continued effect of LAS. The primary outcome was the change in body weight from baseline to treatment endpoint within the intention-to-treat (ITT) analysis. Secondary outcomes contained changes in waist-to-hip ratio (WHR), lipid metabolism, and visceral and subcutaneous adipose tissues. Results: From 14 May 2018 to 03 November 2019, 84 participants out of 201 screened individuals met the eligibility criteria, were randomized, and were analyzed (42 participants in each group). From baseline to treatment endpoint, the body-weight reduction in the LAS group was significantly larger than in the sham control (net difference: 1.57 kg, 95% CI: 0.29-2.86, p = 0.012). The superior weight reduction effect persisted in the follow-up period (net difference: 3.20 kg, 95% CI: 1.17-5.21, p = 0.001). LAS therapy also showed improvement in triglyceride and subcutaneous adipose tissue (SAT) compared with sham control. One participant in the LAS group reported a slightly uncomfortable and tingling sensation after the additional intervention. No other adverse events (AEs) were documented. Conclusion: LAS, a modified acupuncture technique, is safe and effective in body-weight control. It could be used as an alternative choice to classical acupuncture for obesity management. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR1800015498].

Advances in Research on Pharmacological Effect of Astragaloside Ⅳ on Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Astragalus membranaceus has the effect of tonifying Qi and solid surface， diuretic support poison， discharging pus and astringent sores to produce muscle. It is not only used for syndromes such as deficiency of lung and temper， deficiency of spleen and diarrhea， but also for stroke， chest obstruction and other diseases. Due to the complex chemical composition and diverse pharmacological effect of Astragalus membranaceus， and the main role in invigorating qi and activating blood circulation has not been clarified. Astragaloside Ⅳ is one of its main active ingredients. In recent years， more and more studies on Astragaloside Ⅳ have been conducted at home and abroad. It has been reported that it has the medicinal value of enhancing immune function， strengthening heart and lowerin blood glucose， diuresis， anti-aging and anti-fatigue， et al， and has extensive pharmacological activity. Among them， the role of cardiovascular and cerebrovascular diseases in particular has attracted increasing attention. Cardiovascular and cerebrovascular diseases are ischemic or hemorrhagic diseases occurring in the heart， brain and systemic tissues due to blood viscosity， atherosclerosis， hypertension， hyperlipidemia， etc.， including cardiovascular and cerebrovascular diseases. Such diseases are a serious threat to mankind and are the leading cause of death worldwide. At present， western medicine is the main treatment， with many adverse reactions and poor long-term prognosis. TCM believes that the imbalance of qi and blood is the basic pathogenesis of this kind of disease. Qi deficiency and blood stasis are more common.At present， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases in a number of studies， and achieved some results， but this review in recent years， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases play the pharmacological activity， in order to explore whether Astragaloside Ⅳ is the main role of astragalus qi to find a theoretical basis for material basis， but also for the innovation of traditional Chinese medicine drug research and development of theoretical basis and practical guidance.

Roles of processing and compatibility in antidepression of Sini Powder:a metabonomics study / 中国中药杂志

The antidepressant mechanism of Sini Powder was investigated by metabonomics based on UHPLC-Q-TOF-MS, and the roles of processing and compatibility in the antidepression of Sini Powder were discussed in the present study. The chronic unpredictable mild stress(CUMS) model of depression was induced in the model group, the Bupleuri Radix group, the Paeoniae Radix Alba group, the herb-pair group(Bupleuri Radix-Paeoniae Radix Alba), the Sini Powder group, and the vinegar-processed Sini Powder group(Bupleuri Radix and Paeoniae Radix Alba were vinegar-processed). After the establishment of the model, the rats in each group were continuously administered with corresponding drugs(ig) at a dose of 9.6 g·kg~(-1) for eight days [the rats in the model group and the normal group(without model induction) received the same volume of normal saline at the same time]. Following the last administration, the differential metabolites were identified to analyze metabolic pathways based on the rat plasma samples collected from each group. A total of sixteen potential biomarkers were identified. The metabolites with significant changes were involved in many biological metabolic pathways, such as amino acid metabolism, pentose phosphate pathway, glycerol phospholipid metabolism, sphingolipid metabolism, and purine metabolism. After drug intervention, some biomarkers returned to normal levels. Further comparisons of processing and compatibility revealed that the vinegar-processed Sini Powder group had the most total metabolic pathways where differential metabolites were returned to normal. Compared with the individual herbs, the herb-pair significantly improved the recovery of differential metabolites in the pentose phosphate and purine metabolic pathways. Compared with the Sini Powder, the vinegar-processed Sini Powder facilitated the recovery of differential metabolites in the arginine biosynthesis, and pyrimidine and pentose phosphate metabolic pathways. As indicated by the results, Sini Powder may interfere with depression by regulating lipid and nucleotide metabolisms. The processing and compatibility of Chinese herbal medicines can potentiate the intervention on depression by regulating nucleotide, energy, and amino acid metabolisms to a certain extent.

Modern Pharmacological Toxicology and Clinical Application of Antitumor Nanometer Realgar / 中国实验方剂学杂志

Realgar is toxic and belongs to drug of poison attack, with anti-cancer, anti-pest, dry wet and expectorant effects. Ancient doctors often used realgar to treat carbuncle, boil, abdominal pain and other diseases. Modern doctors use it to treat malignant tumors and blood diseases. The toxicity of realgar results in a small range of safety in its drug use. Modern scholars combine traditional Chinese medicine with nano-technology means to grind realgar into nano-realgar. Compared with realgar, nano-realgar has an improved bioavailability and reduced toxicity in vivo. Modern pharmacological researches use nano-realgar to interven lung cancer cells, skin cancer cells, cervical cancer cells, ovarian cancer cells and leukemia cells in experiments, which confirmed that nano-realgar has effects in inhibiting cell proliferation, inducing apoptosis and cell differentiation, inhibiting nucleic acid synthesis and angiogenesis, but with antiviral, sterilization of analgesic effects. Modern toxicological studies have been conducted in mice through intragastric treatment with different concentrations of nano-realgar preparation. The symptoms and signs of mice and various auxiliary examination indexes were recorded at different time periods. It was concluded that nano-realgar has regular effects on blood biochemical indexes at safe doses. In clinical trials, nano-realgar was applied to treat damaged wound surface of malignant tumor. It was found that nano-realgar can promote healing of wound surface of tumor, alleviate pain, relieve clinical symptoms, such as bleeding, purulence and odor, and improve quality of life of patients. In addition, with a simple usage and good patient compliance, administration with nano-realgar requires no hospitalization, can save medical resources, and is worthy of clinical promotion and application.

Research progress on antidepressant effects of Sini San based on three progressive levels of "single herb, herb-pair, and complicated Chinese herbal formula" / 中国中药杂志

Depression is a kind of mental illness accompanied by complex etiology and pathogenesis in clinic. With the quickening pace of circadian rhythm and increase of life pressure in modern society, the incidence of depression is increasing year by year. Nowadays, some typical antidepressant Western medicines, such as selective serotonin re-uptake inhibitors (SSRI) and tricyclic antidepressants (TCA), have been used as the main therapeutic drugs in clinic. Unfortunately, administration of these drugs will result in severe adverse reactions, slow treatments, and low cure rates, thus obviously they can not be used for a long term. Sini San, which originated from written by Zhang zhongjing, is a prescription widely applied in clinic for curing mental illness and also a basic Chinese herbal formula for modern treatment of depression. This article would review the research progress on antidepressant effects of Sini San based on single herbs of Bupleuri Radix and Paeoniae Radix Alba, herb-pair of Bupleuri Radix-Paeoniae Radix Alba, and formula of Sini San, providing directions and ideas for future research on complicated Chinese herbal formulae.

A new strategy for exploring herb-pair investigation with a case study on Astragali Radix-Corni Fructus in treatment of diabetic nephropathy / 中国中药杂志

As the smallest unit of traditional Chinese medicinal formula compatibility, herb-pair has the basic characteristic of traditional Chinese medicinal formula compatibility. In recent years, herb-pair investigation has attracted much attention, which is an indispensable part of modernization of traditional Chinese medicine. With the decrease of the efficiency in the discovery of new drug, how to discover new drugs from traditional Chinese medicinal herb-pair has also been a bottleneck for the research and development of drug. The authors reviewed the domestic and foreign literatures in the latest years and summarized the current situations and the existing problems of herb-pair study. Based on these investigations, the authors innovatively proposed a novel concept of "precision herb-pair". Difference from traditional Chinese medicinal herb-pair or formulae with extensive roles and unclear efficacies, "precision herb-pair" belongs to a developed new mini herb-pair formula with an exact treatment and a relatively clear composition based on a certain specific disease. In addition, the authors also proposed a new strategy of "herb-pair - screen of multiple constituents based on column separation and in vitro cell viability - fuzzy target recognition pharmacology - re-evaluation of precision herb-pair", and successfully applied it to the development of a precision herb-pair from Astragali Radix-Corni Fructus in treatment of diabetic nephropathy. This proposed new strategy is simple, easy to carry out, and has a wide application, and can offer references and thoughts for the modern investigation of herb-pair and the research and development of new drug.

Establishment and application of HPLC-QAMS for quality evaluation of Chuanxiong Rhizoma / 药学学报

A quantitative analysis method of multi-components with a single marker (QAMS) for simultaneous determination of six marker compounds (one from phenolic acids and five from phthalides) in Chuanxiong Rhizoma was established by applying HPLC and using butylidenephthalide as the internal reference substance. And also the feasibility and accuracy of the established method for quality evaluation and application of Chuanxiong Rhizoma were investigated and validated. The analysis was performed with the mobile phase consisting of acetonitrile - 0.2% aqueous formic acid. The flow rate was 1.0 mL . min-1 and the column temperature was maintained at 30 °C. The detection wavelengths were set at 252 nm (for ferulic acid, Z-ligustilide, and butylidenephthalide) and 266 nm (for senkyunolide I, senkyunolide A, and coniferyl ferulate), separately, and 20 µL was injected for analysis with gradient elution. The results showed that there were no significant differences observed between the HPLC-QAMS method and the external standard method (RSD <5%). The relative correction factors were credible (RSD < 5%) in changed chromatographic conditions. The established HPLC-QAMS method can be accurately used for simultaneously evaluating and controlling the quality of Chuanxiong Rhizoma with multi-components.