Salvianolic Acid B: A Review of Pharmacological Effects, Safety, Combination Therapy, New Dosage Forms, and Novel Drug Delivery Routes.

Salvianolic acid B is extracted from the roots and rhizomes of Danshen (Salvia miltiorrhiza Bge., family Labiatae). It is a water-soluble, weakly acidic drug that has demonstrated antitumor and anti-inflammatory effects on various organs and tissues such as the lung, heart, kidney, intestine, bone, liver, and skin and protective effects in diseases such as depression and spinal cord injury. The mechanisms underlying the protective effects of salvianolic acid B are mainly related to its anti-inflammatory, antioxidant, anti- or pro-apoptotic, anti- or pro-autophagy, anti-fibrotic, and metabolism-regulating functions. Salvianolic acid B can regulate various signaling pathways, cells, and molecules to achieve maximum therapeutic effects. This review summarizes the safety profile, combination therapy potential, and new dosage forms and delivery routes of salvianolic acid B. Although significant research progress has been made, more in-depth pharmacological studies are warranted to identify the mechanism of action, related signaling pathways, more suitable combination drugs, more effective dosage forms, and novel routes of administration of salvianolic acid B.

Chemical constituents, pharmacological action, antitumor application, and toxicity of Strychnine Semen from Strychnons pierriana A.W.Hill.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried and mature seeds of Strychnons pierriana A.W.Hill. have been called Strychnine Semen(S. Semen). It have been used in traditional Chinese medicine for nearly 400 years. In recent decades, scholars at home and abroad have widely used S. Semen in the treatment of tumor diseases, showing good anti-tumor effects. In this paper, the modern research achievements of S. Semen are reviewed, including traditional uses, phytochemistry, pharmacology, and toxicology. AIM OF THE STUDY: In recent years, the research on S. Semen has increased gradually, especially the research on its anti-tumor. This paper not only reviewed the traditional uses, chemical constituents and pharmacological activities of S. Semen, but also comprehensively listed the mechanisms of Strychnos in the treatment of different tumors, providing a review for further research and development of Strychnos resources. MATERIALS AND METHODS: A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases. RESULTS: The main constituents of S. Semen include alkaloids, terpenoids, steroids, and their glycosides. Modern studies have proved that S. Semen has a wide range of pharmacological effects, including anti-inflammatory and analgesic, anti-thrombotic, myocardial cell protection, immune regulation, nerve excitation, and anti-tumor effects. Among them, the anti-tumor effect has been the focus of research in recent years. S. Semen have a certain therapeutic effect on many kinds of tumors, such as liver cancer, colon cancer, and stomach cancer in the digestive system, breast, cervical, and ovarian cancer in the reproductive system, myeloma and leukemia in the blood system, and those in the nervous system and the immune system. CONCLUSION: Strychnine has an inhibitory effect on a variety of tumors. However, modern studies of strychnine are incomplete, and more in-depth studies are needed on its stronger bioactive constituents and potential pharmacological effects. The antitumor effect of Strychnine is worth further exploration.

Effectiveness and Safety of Traditional Chinese Medicine in Treatment of Primary Sjögren's Syndrome Patients: A Meta-analysis.

BACKGROUND: Primary Sjögren's Syndrome (pSS) is an autoimmune disease. It can damage the salivary and lacrimal glands and is characterized by dry mouth and eye symptoms, which seriously affects people's normal life. Both modern medicine and Traditional Chinese medicine (TCM) have certain effects in treating SS. However, there are different theories about which treatment is more appropriate. OBJECTIVE: The aim of this research was to compare the efficacy and safety of TCM to Western Medicine in the treatment of pSS. METHODS: We collected randomized controlled trials (RCTs) of TCM, integrating traditional Chinese and Western medicine for the treatment of pSS in Chinese and foreign databases. RESULTS: A total of 13 articles were eventually included with 780 cases. The final results were expressed in odds ratio (OR), mean difference (MD), 95% confidence interval (CI), and overall effect (z). The effective rate was 86.03% in the TCM group and 67.75% in the western medicine group. Results of the effective rate were OR = 3.57; 95% CI = 2.44-5.23; z = 6.56; p＜0.00001, ESR were MD = -6.90; 95% CI = -10.76--3.05; z = 3.51; p = 0.0005＜0.05, Schirmer's test were MD = 3.39; 95% CI = 1.92-4.86; z = 4.5; p＜0.00001, salivary flow were MD = 0.62; 95% CI = 0.16-1.07; z = 2.63; p = 0.009＜0.05, and adverse reactions were OR = 0.35; 95% CI = 0.17-0.72; z = 2.84; p = 0.004. CONCLUSION: TCM has a remarkable effect on the treatment of pSS. Among them Yiguanjian decoction and Liuwei Dihuang decoction were effective prescriptions with the highest frequency of application. Rehmanniae Radix (Rehmannia glutinosa Libosch.) and Ophiopogonis Radix (Ophiopogon japonicus (L. f.) Ker-Gawl.) were the most frequently used TCM.

Effect of a combination of Atractylodes macrocephala extract with strychnine on the TLR4/NF-κB/NLRP3 pathway in MH7A cells.

Rheumatoid arthritis (RA) is now widely recognized as a chronic systemic inflammatory autoimmune disease characterized by swelling, pain and stiffness, which are often disabling. Although the number of drugs available for the treatment of RA has increased in recent years, they are generally expensive, leave patients prone to relapse and can result in severe effects when discontinued. Thus, there is a need for an inexpensive drug with fewer side effects that can be adhered to relieve pain and slow down the progression of the disease. Strychnine, a traditional Chinese medicine, was often used in ancient times to treat swollen and painful joints; however, because of its somewhat toxic nature, it is often combined with Atractylodes macrocephala to reduce its toxicity for safer therapeutic action. The present study performed high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) analysis to confirm whether the use of strychnine with Atractylodes macrocephala had the effect of reducing strychnine content. MH7A cells were induced using IL-1ß to study the effect of strychnine with Atractylodes macrocephala on the Toll-like receptor 4 (TLR4)/NF-κB/NLR family pyrin domain-containing 3 (NLRP3) pathway in order to verify its role in the treatment of RA. The results indicated that the combined application of HPLC-MS/MS strychnine and Atractylodes macrocephala had a reducing effect on the strychnine content. From the subsequent experimental results, it can be inferred that Strychnine combined with Atractylodes macrocephala extract could promote the apoptosis of synovial cells, and could inhibit the expression levels of TLR4, NF-κB and NLRP3 in the cells as well as reducing the MH7A-positive cells. The expression levels of TLR4, IκB kinase ß, NF-κB and NLRP3 were significantly reduced after treatment with each administration group, resulting in a decrease in the phosphorylation levels of TLR4 and NF-κB, indicating that the combination potently inhibited their phosphorylation. The combination of strychnine and atractylenolide II was also revealed to be the main active ingredient in the treatment of RA.

Chemical constituents, pharmacological effects, toxicology, processing and compatibility of Fuzi (lateral root of Aconitum carmichaelii Debx): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The lateral root of Aconitum carmichaelii Debx is known as Fuzi in Chinese. It is traditionally valued and used for dispelling cold, relieving pain effects, restoring 'Yang,' and treating shock despite its high toxicity. This review aims to provide comprehensive information on the chemical composition, pharmacological research, preparation, and compatibility of Fuzi to help reduce its toxicity and increase its efficiency, based on the scientific literature. In addition, this review will establish a new foundation for further studies on Fuzi. MATERIALS AND METHODS: A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases. RESULTS: Fuzi extracts contain diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloids types, and have various pharmacological activities, such as strong heart effect, effect on blood vessels, and antidepressant, anti-diabetes, anti-inflammatory, pain-relieving, antitumor, immunomodulatory, and other therapeutic effects. However, these extracts can also lead to various toxicities such as cardiotoxicity, neurotoxicity, reproductive toxicity, hepatotoxicity, and embryonic toxicity. In vivo and in vitro experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Fuzi. CONCLUSION: The therapeutic potential of Fuzi has been demonstrated in conditions, such as heart failure, various pains, inflammation, and tumors, which is attributed to the diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloid types. In contrast, they are also toxic components. Proper processing and suitable compatibility can effectively reduce toxicity and increase the efficiency of Fuzi. Thus more pharmacological and toxicological mechanisms on main active compounds are necessary to be explored.

The isolation, structural features and biological activities of polysaccharide from Ligusticum chuanxiong: A review.

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.

Identifying the mechanisms and molecular targets of Hongjingtian injection on treatment of TGFß1-induced HK-2 cells: coupling network pharmacology with experimental verification.

Background: The study was designed to investigate the mechanism of Hongjingtian injection (HJT) in treating tubulointerstitial fibrosis (TIF) in chronic kidney diseases (CKD) based on network pharmacology and experimental verification. Methods: First, active ingredients of HJT obtained from literature were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and putative targets of active ingredients were predicted using the Chemmapper, SEA and Swiss Target Prediction database. Subsequently, the "compound-target" network for HJT was established. In addition, TIF disease targets were obtained from the GEO gene chips (accession number GSE20247). The intersecting targets of HJT and TIF obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, quantitative polymerase chain reaction (qPCR) and Western blot (WB) were used to validate the predicted five key genes targets (GAD1, SPHK1, P4HA2, AKR1B1, PTGES). And immunofluorescence, wound healing assay and transwell assay were used to verify the anti-fibrosis effect of HJT on TGFß1-induced HK-2 cells. Results: The network pharmacology analysis results showed that there are 36 active compounds and 1,044 putative target genes in HJT. HJT may exert its inhibitory effects against TIF by acting on 79 key targets. Besides, KEGG analysis indicated that the anti-TIF effect of HJT was mediated by multiple pathways, such as the metabolic pathway, pathways in cancer and gap junction. Among them, GAD1, SPHK1, P4HA2, AKR1B1 and PTGES are enriched in the metabolic pathway. In vitro induced cell model experiments, the immunofluorescence experience showed that HJT could restore EMT of HK-2 cells. In addition, the qPCR and WB results showed that HJT significantly restored the expression of the SPHK1 in HK-2 cells induced by TGF-ß1. Conclusions: This study comprehensively illuminated the active compounds, potential targets, and molecular mechanism of HJT against TIF. HJT treatment of TIF may reverse EMT caused by TGF-ß1 by targeting SPHK1.

Mechanism of Action of Strychni Semen for Treating Rheumatoid Arthritis and Methods for Attenuating the Toxicity.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which affects the joints and causes significant pain, impairing patient's quality of life. Strychni semen showed promising results to treat RA. However, there are increasing safety concerns in using strychni semen due to its severe toxicity. AIM AND OBJECTIVE: The purpose of this review is to provide insight into using Strychni semen as an alternative medicine to treat RA, as well as to offer a method for the safe application of Strychni semen through processing and compatibility studies. METHODS: Publications were retrieved and surveyed from CNKI and PubMed relevant to Strychni semen for a literature review. RESULTS: This article summarized the mechanism of function of strychni semen in treating RA with its anti-inflammatory, analgesic, and immunomodulatory effect. Commonly used methods to attenuate the toxicity of Strychni semen were also discussed in this article. CONCLUSION: Strychni semen has a good therapeutic effect on RA, mainly by the modulation of immunity with anti-inflammatory and analgesic effects. Also, the reported toxicity of strychni semen can be effectively reduced by processing and compatibility methods. Hence, as an alternative medicine for RA treatment, strychni semen has a broad prospect.

Experimental Study on the Effect of Aconite and Angelica sinensis on Myocardial Ischemia Rats with Yang Deficiency and Blood Stasis.

OBJECTIVE: To investigate the intervention effect and mechanism of Aconite and Angelica sinensis on myocardial ischemia rats with Yang deficiency and blood stasis. METHODS: SPF-class SD rats were randomly divided into low-dose and high-dose groups. Each group was divided into control group, model group, and drug-administered group (FZ, DG, FG; 1 : 0.5, 1 : 1, 1 : 2). A rat model was prepared by intraperitoneal injection of hydrocortisone and isoproterenol plus cold stimulation. Each group was given corresponding decoction or distilled water for 14 days. The behavioral changes of rats in each group were observed. The morphological changes of rats cardiomyocytes were observed by HE staining. The average optical density (MOD value) and percentage of positive cells of Bcl-2, Bax, and Akt were determined by immunohistochemical staining method, and PEIs were calculated. Western blot and RT-PCR were used to determine the expression of PI3K, Caspase-3, Akt protein, and gene expression. RESULTS: The compatibility of Aconite and Angelica sinensis improved the morphology of rat cardiomyocytes, increased the PEI values of Akt and Bcl-2 protein, and decreased the PEI values of Bax protein (P < 0.01). The compatibility reduced the expression of Caspase-3 protein of rat myocardium and increased the protein expression of p-Akt, PI3K, and p-PI3K (P < 0.01). The compatibility also significantly reduced the expression of Caspase-3 mRNA and increased the expression of PI3K mRNA and Akt mRNA (P < 0.05 or P < 0.01), and the effect of high-dose FG (1 : 2) group is the best. CONCLUSIONS: The method of preparing a rat model of myocardial ischemia with Yang deficiency and blood stasis was feasible. The compatibility of Aconite and Angelica sinensis reduced myocardial fibrosis and inflammatory reaction, protected ischemic cardiomyocytes, and reduced myocardial injury, whose mechanism may be related to the regulation of PI3K/Akt pathway. The compatible group had better intervention effects than Aconite or Angelica sinensis alone. The best one was high-dose FG (1 : 2).

Zinc effects on cadmium toxicity in two wheat varieties (Triticum aestivum L.) differing in grain cadmium accumulation.

Presence of cadmium (Cd) in food poses serious risks to human health. Understanding the effects of zinc (Zn) on Cd absorption by crops could help provide a theoretical basis for the treatment with Zn on contaminated soils. In this study, two wheat varieties, differing in grain-Cd accumulation ability (L979, a Cd low-accumulation variety, and H27, a high-accumulation variety) were selected to investigate the effect of Zn addition on Cd toxicity. Cd was applied to nutrient solutions at 0 and 10 µM, and added Zn were 0, 50 and 100 µM. Zn supplements alleviated decreases in biomass induced by Cd toxicity for both varieties, and both varieties had different reduced concentrations of Cd in their shoots. Application of 50 µM Zn to H27 resulted in a 17% decrease in Cd concentrations. When treated with 100 µM Zn, only L979 showed a reduction in Cd concentration. The higher proportion of Cd in the soluble fraction was found in L979. In addition, ion-selective scanning at the root-surface indicated that Zn supplements reduced net root Cd2+ flux by 55% for L979, and 69% for H27. These mitigating effects of Zn in both varieties involved mechanisms related to photosynthesis, root growth, and antioxidant production. Additionally, both Zn available in the medium and absorbed in plant tissue causes antagonistic effects on Cd absorption for wheat. It seemed that vacuolar compartmentation could contribute Cd detoxification especially for low accumulation variety.

Expression and function analysis of mitotic checkpoint genes identifies TTK as a potential therapeutic target for human hepatocellular carcinoma.

The mitotic spindle checkpoint (SAC) genes have been considered targets of anticancer therapies. Here, we sought to identify the attractive mitotic spindle checkpoint genes appropriate for human hepatocellular carcinoma (HCC) therapies. Through expression profile analysis of 137 selected mitotic spindle checkpoint genes in the publicly available microarray datasets, we showed that 13 genes were dramatically up-regulated in HCC tissues compared to normal livers and adjacent non-tumor tissues. A role of the 13 genes in proliferation was evaluated by knocking them down via small interfering RNA (siRNA) in HCC cells. As a result, several mitotic spindle checkpoint genes were required for maintaining the proliferation of HCC cells, demonstrated by cell viability assay and soft agar colony formation assay. Then we established sorafenib-resistant sublines of HCC cell lines Huh7 and HepG2. Intriguingly, increased TTK expression was significantly associated with acquired sorafenib-resistance in Huh7, HepG2 cells. More importantly, TTK was observably up-regulated in 46 (86.8%) of 53 HCC specimens. A series of in vitro and in vivo functional experiment assays showed that TTK overexpression promoted cell proliferation, anchor-dependent colony formation and resistance to sorafenib of HCC cells; TTK knockdown restrained cell growth, soft agar colony formation and resistance to sorafenib of HCC cells. Collectively, TTK plays an important role in proliferation and sorafenib resistance and could act as a potential therapeutic target for human hepatocellular carcinoma.