Cinobufagin: a promising therapeutic agent for cancer.

OBJECTIVES: Cinobufagin is a natural active ingredient isolated from the traditional Chinese medicine Venenum Bufonis (Chinese: Chansu), which is the dried secretion of the postauricular gland or skin gland of the Bufo gargarizans Cantor or Bufo melanostictus Schneider. There is increasing evidence indicating that cinobufagin plays an important role in the treatment of cancer. This article is to review and discuss the antitumor pharmacological effects and mechanisms of cinobufagin, along with a description of its toxicity and pharmacokinetics. METHODS: The public databases including PubMed, China National Knowledge Infrastructure and Elsevier were referenced, and 'cinobufagin', 'Chansu', 'Venenum Bufonis', 'anticancer', 'cancer', 'carcinoma', and 'apoptosis' were used as keywords to summarize the comprehensive research and applications of cinobufagin published up to date. KEY FINDINGS: Cinobufagin can induce tumour cell apoptosis and cycle arrest, inhibit tumour cell proliferation, migration, invasion and autophagy, reduce angiogenesis and reverse tumour cell multidrug resistance, through triggering DNA damage and activating the mitochondrial pathway and the death receptor pathway. CONCLUSIONS: Cinobufagin has the potential to be further developed as a new drug against cancer.

An endophytic fungus Schizophyllum commune isolated from Panax ginseng enhances hairy roots growth and ginsenoside biosynthesis.

Using endophytic fungal elicitors to increase the accumulation of valuable secondary metabolites in plant tissue culture is an effective biotechnology strategy. In this study, a collection of 56 strains of endophytic fungi were isolated from different organs of cultivated Panax ginseng, of which seven strains can be symbiotically co-cultured with the hairy roots of P. ginseng. Further experiments observed that strain 3R-2, identified as endophytic fungus Schizophyllum commune, can not only infect hairy roots but also promote the accumulation of specific ginsenosides. This was further verified because S. commune colonization significantly affected the overall metabolic profile of ginseng hairy roots. By comparing the effects of S. commune mycelia and its mycelia extract (EM) on ginsenoside production in P. ginseng hairy roots, the EM was confirmed to be a relatively better stimulus elicitor. Additionally, the introduction of EM elicitor can significantly enhance the expressions of key enzyme genes of pgHMGR, pgSS, pgSE, and pgSD involved in the biosynthetic pathway of ginsenosides, which was deemed the most relevant factor for promoting ginsenosides production during the elicitation period. In conclusion, this study is the first to show that the EM of endophytic fungus S. commune can be considered as an effective endophytic fungal elicitor for increasing the biosynthesis of ginsenosides in hairy root cultures of P. ginseng.

Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents.

BACKGROUND: Macrophages are one of the major cell types in the immune system and are closely related to tumor development, which can be polarized into M1 type with anti-tumor activity or M2 type with pro-tumor activity. The infiltration of more macrophages into tumor predicts poorer prognosis due to their more exhibition of M2 phenotype under the influence of many factors in the tumor microenvironment (TME). Therefore, reverse of M2 macrophage polarization in TME is conducive to the suppression of tumor deterioration and understanding the influencing factors of macrophage polarization is helpful to provide new ideas for the subsequent targeting macrophages for tumor therapy. PURPOSE: This review summarizes the effects of TME on macrophage polarization and natural products against M2 macrophage polarization, which may provide some directions for tumor therapy. METHODS: The search of relevant literature was conducted using the PubMed, Science Direct, CNKI and Web of Science databases with the search terms "macrophage", "tumor microenvironment", "natural product" and "tumor". RESULTS: The mutual transformation of M1 and M2 phenotypes in macrophages is influenced by many factors. Tumor cells affect the polarization of macrophages by regulating the expression of genes and proteins and the secretion of cytokines. The expression of some genes or proteins in macrophages is also related to their own polarization. Many natural products can reverse M2 polarization of macrophages which has been summarized in this review. CONCLUSION: Regulation of macrophage polarization in TME can inhibit tumor development, and natural products have the potential to impede tumor development by regulating macrophage polarization.

Herbal medicines for insomnia through regulating 5-hydroxytryptamine receptors: a systematic review / 中国天然药物

Insomnia is a common sleep disorder without effective therapy and can affect a person's life. The mechanism of the disease is not completely understood. Hence, there is a need to understand the targets related to insomnia, in order to develop innovative therapies and new compounds. Recently, increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia. Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain. In this review, the role of 5-hydroxytryptamine (5-HT) in insomnia development is summarized, while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes, in order to provide reference for subsequent research.

Isatis indigotica: a review of phytochemistry, pharmacological activities and clinical applications.

OBJECTIVES: Isatis indigotica Fort. (I. indigotica) is an herbaceous plant belonging to Cruciferae family. Its leaf (IIL) and root (IIR) are commonly used in traditional Chinese medicines (TCMs) with good clinical efficacies such as clearing away heat and detoxification, cooling blood and reducing swelling. This review aimed to provide a systematic summary on the phytochemistry, pharmacology and clinical applications of I. indigotica. KEY FINDINGS: This plant contains alkaloids, organic acids, flavonoids, lignans, nucleosides, amino acids, and steroids. Previous pharmacological researches indicated that I. indigotica possesses promising antivirus, antibacterial, immunoregulatory, anti-inflammation, and cholagogic effects. Importantly, it can inhibit various viruses, such as influenza, hepatitis B, mumps, herpes simplex, cytomegalovirus, and coxsachievirus. Clinically, it is frequently used to treat various viral diseases like viral influenza, parotitis and viral hepatitis. Consequently, I. indigotica may be beneficial for the prevention and treatment of coronavirus disease 2019 (COVID-19). SUMMARY: This paper reviewed the chemical constituents, pharmacological effects and clinical applications of I. indigotica which may guide further research and application of this plant.

Transcription Factor: A Powerful Tool to Regulate Biosynthesis of Active Ingredients in Salvia miltiorrhiza.

Salvia miltiorrhiza Bunge is a common Chinese herbal medicine, and its major active ingredients are phenolic acids and tanshinones, which are widely used to treat vascular diseases. However, the wild form of S. miltiorrhiza possess low levels of these important pharmaceutical agents; thus, improving their levels is an active area of research. Transcription factors, which promote or inhibit the expressions of multiple genes involved in one or more biosynthetic pathways, are powerful tools for controlling gene expression in biosynthesis. Several families of transcription factors have been reported to participate in regulating phenolic acid and tanshinone biosynthesis and influence their accumulation. This review summarizes the current status in this field, with focus on the transcription factors which have been identified in recent years and their functions in the biosynthetic regulation of phenolic acids and tanshinones. Otherwise, the new insight for further research is provided. Finally, the application of the biosynthetic regulation of active ingredients by the transcription factors in S. miltiorrhiza are discussed, and new insights for future research are explored.

Isorhamnetin: A review of pharmacological effects.

Isorhamnetin is one of the most important active ingredients in the fruits of Hippophae rhamnoides L. and the leaves of Ginkgo biloba L., which possesses extensive pharmacological activities. At present, there have been numerous investigations on isorhamnetin, which has the effects of cardiovascular and cerebrovascular protection, anti-tumor, anti-inflammatory, anti-oxidation, organ protection, prevention of obesity, etc. The related mechanisms involve the regulation of PI3K/AKT/PKB, NF-κB, MAPK and other signaling pathways as well as the expression of related cytokines and kinases. Isorhamnetin has a high value of development and application. However, the investigations on its mechanism of action are limited and lack of detailed scientific validation. The manuscript reviewed the pharmacological effects of isorhamnetin and related mechanisms of action for the development of its medicinal properties further.

Beneficial Effects of Endophytic Fungi from the Anoectochilus and Ludisia Species on the Growth and Secondary Metabolism of Anoectochilus roxburghii.

Endophytic fungi possess favorable effects on their host plants, including disease-resistance improvement, secondary metabolite induction, and growth promotion. It is therefore a promising and sustainable strategy to utilize endophytic fungi for the quality improvement of medicinal herbs or important crops. In our study, a collection of 277 strains of endophytic fungi were isolated from Anoectochilus and Ludisia orchids. Two strains J162 and J211 can be symbiotically cocultured with the tissue culture seedlings of Anoectochilus roxburghii, a popular medicinal and edible plant in southern China. Both strains can significantly enhance the biomass of A. roxburghii and induce the biosynthesis and accumulation of its active ingredients, including flavonoids, kinsenoside, and polysaccharides. J162 and J211 were further identified as Chaetomium globosum and Colletotrichum gloeosporioides based on multilocus phylogenetic analysis. Immunocytochemical staining indicated that J162 and J211 mainly colonized the intercellular gap of xylem parenchyma cells of A. roxburghii roots without obvious harm. In addition, quantitative real-time polymerase chain reaction showed that the expression of three growth-related genes, namely, uracil phosphoribosyl transferase, amino acid transmembrane transporter, and maturase K, were significantly altered in A. roxburghii plants when treated with J162 and J211. In conclusion, the two strains are highly beneficial microbial resources for the growth and accumulation of active ingredients of A. roxburghii in agricultural cultivation.

Compound-based Chinese medicine formula: From discovery to compatibility mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese medicine formula (CMF) has a long history of clinical use in the treatment of various diseases under the guidance of traditional Chinese medicine (TCM) theory. The application of CMF can be divided into three levels, crude extracts, homologous compounds mixture, and specific compounds. However, the modern scientific connotation of the CMF theory has not been clarified. AIM OF THE REVIEW: To critically evaluate the research strategy for the investigation of compound-based CMF (CCMF). MATERIALS AND METHODS: The related information was collected from the scientific databases, including CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Web of Science, and Wiley Online. RESULTS: The research design including discovery, screening, optimization, pharmacodynamics models, and target research techniques including the targets for compatibility compounds were evaluated. Essentially it has been evaluated that the in vitro multicellular three-dimensional culture or organoid model has been proposed for the optimization model for compatibility research of CCMF. Based on these, the traditional compatibility theory of CMF, such as Monarch-Minister-Assistant-Guide (Jun-Chen-Zuo-Shi in Chinese), can probably be elucidated by the CCMF research. CONCLUSIONS: CCMF has the clear advantage of providing the exact composition and controllable quality of modern medicines, in addition to having the characteristics of multi-ingredients and multi-targets synergistic effects of TCM. However, CCMF is still associated with challenges which need to be addressed for its future use.

Scutellaria barbata: A Review on Chemical Constituents, Pharmacological Activities and Clinical Applications.

Scutellaria barbata has a long history of medical use in Traditional Chinese Medicine for removing heat and toxic material, promoting blood circulation and removing blood stasis, and inducing diuresis to reduce edema. Recent pharmacology investigations have provided evidence for its anti-cancer, bacteriostasis, anti-virus, anti-inflammation, anti-oxidation and immunity enhancement properties. The efficacy of activating blood circulation and removing blood stasis has unique advantages in the treatment of cardiovascular and cerebrovascular diseases. A total of 84 compounds have been isolated from S. barbata and are characterized mainly as flavonoids, diterpenoids, followed by polysaccharide, volatile oil and steroids. Peer-reviewed articles published over the last few years were gathered by consulting the databases PubMed, Elsevier, Springer, and Chinese Herbal Classics. This review mainly focuses on the pharmacologically active constituents isolated from S. barbata，which have been subjected to in vitro and/or in vivo studies. Although, the chemical components, pharmacological activities, toxicology, clinical applications and mechanisms of action of S. barbata have been investigated, many constituents remain unknown. Further investigations are required to investigate the medicinal properties of S. barbata.

Cynanchum bungei Decne and its two related species for "Baishouwu": A review on traditional uses, phytochemistry, and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum bungei Decne. (CB) (Asclepiadaceae) and its two related species Cynanchum auriculatum Royle ex Wight. (CA) and Cynanchum wilfordii (Maxim.) Hemsl. (CW) are well known Chinese herbal medicines known by the name Baishouwu. Among them, CB has long been used for nourishing the kidney and liver, strengthening the bones and muscles, and regulating stomachache. However, to date, no comprehensive review on Baishouwu has been published. AIM OF THE REVIEW: This review aims to provide a comprehensive summary on traditional uses, phytochemistry, pharmacology, and toxicology of the three herbal components of Baishouwu with the ultimate objective of providing a guide for future scientific and therapeutic potential use of Baishouwu. MATERIAL AND METHODS: A literature search was undertaken on CB, CA and CW by analyzing the information from scientific databases (SciFinder, Pubmed, Elsevier, Google Scholar, Web of Science, and Baidu Scholar). Information was also gathered from local classic herbal literatures and conference papers on ethnopharmacology and the information provided in this review has been obtained from peer-reviewed papers. RESULTS: Comparative analysis of literature search indicate that ethnopharmacological use of CB was recorded in China, however, CA and CW have been used in China, Korea and Japan. To date, 151 chemical compounds have been isolated from these species, and the major chemical constituents have been revealed to be acetophenones, C21-steroids, terpenoids, and alkaloids. These compounds and extracts have been proven to exhibit significant pharmacological activities, including anti-tumor, anti-inflammatory, immunomodulatory, hypolipidemic, anti-obesity, hepatoprotective, antifungal, antiviral, anti-depressant, vasodilating and estrogenic activities. CONCLUSIONS: CB, CA and CW collectively known as Baishouwu are valuable medicinal herbs with multiple pharmacological activities. The traditional use for nourishing liver is closely associated with the hepatoprotective activity. The available literature performs that various of the activity of Baishouwu can be attributed to acetophenones and C21-steroids. It is high time that more efforts should be focused on the underlying mechanisms of their beneficial bioactivities and the structure activity relationship of the constituents, as well as their potential synergistic and antagonistic effects. The proper toxicology evaluation is crucial to guarantee the safety, efficacy, and eligibility for medical use. Further research on the comprehensive evaluation of medicinal quality and the understanding of multi-target network pharmacology of Baishouwu is in great request.

Therapeutic effect of Dongbai-Tonglin-Fang, a Chinese herbal formula, on urinary tract infection in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has many obvious advantages in the treatment of chronic conditions such as urinary tract infection (UTI). Dongbai-Tonglin-Fang (DBTL), a Chinese herbal formula, has been used for the treatment of UTI for more than 40 years with proven efficacy. However, its mechanism of action is still unknown. AIM OF THE STUDY: The purpose of this study is to evaluate the therapeutic efficacy of DBTL and its mechanism of action in a rat UTI model. MATERIALS AND METHODS: E. coli solution induced UTI rat model was used to evaluate the therapeutic effect of DBTL on UTI. Biochemical indicators related to UTI were measured. The kidney tissue was stained with hematoxylin-eosin (HE) to observe pathological changes whilst the ear swelling, feet swelling, hot plate and body torsion tests were used to estimate the anti-inflammatory and analgesic effects of DBTL. RESULTS: After treatment with different doses of DBTL (1, 2, 4 g/kg), a decrease in weight of the kidney in the UTI rat model was observed. The contents of white blood cell, nitrite, urinary albumin, ketone body, bilirubin and occult blood in the urine were also reduced whilst an increase in the pH of urine was observed. HE staining showed that the pathological changes in the kidney tissue were alleviated. At the same time, ear swelling assay showed that the weight and the degree of swelling of the ear of the mice in DBTL groups were decreased remarkably. DBTL also reduced the degree of feet swelling of the rats caused by the adjuvant. Furthermore, with the DBTL treatment, the latency period of foot licking induced by thermal stimulation was increased while the number of twists was lessened. CONCLUSION: These results show that DBTL has an excellent therapeutic effect on UTI rats accompanying with anti-inflammation and analgesia. The data presented here lays the foundations for further investigations in the treatment of UTI.

Diverse Pharmacological Activities and Potential Medicinal Benefits of Geniposide.

Geniposide is a well-known iridoid glycoside compound and is an essential component of a wide variety of traditional phytomedicines, for example, Gardenia jasminoides Elli (Zhizi in Chinese), Eucommia ulmoides Oliv. (Duzhong in Chinese), Rehmannia glutinosa Libosch. (Dihuang in Chinese), and Achyranthes bidentata Bl. (Niuxi in Chinese). It is also the main bioactive component of Gardeniae Fructus, the dried ripe fruit of Gardenia jasminoides Ellis. Increasing pharmacological evidence supports multiple medicinal properties of geniposide including neuroprotective, antidiabetic, hepatoprotective, anti-inflammatory, analgesic, antidepressant-like, cardioprotective, antioxidant, immune-regulatory, antithrombotic, and antitumoral effects. It has been proposed that geniposide may be a drug or lead compound for the prophylaxis and treatment of several diseases, such as Alzheimer's disease, Parkinson's disease, diabetes and diabetic complications, ischemia and reperfusion injury, and hepatic disorders. The aim of the present review is to give a comprehensive summary and analysis of the pharmacological properties of geniposide, supporting its use as a medicinal agent.

Prunella vulgaris: A Comprehensive Review of Chemical Constituents, Pharmacological Effects and Clinical Applications.

Prunella vulgaris (PV) is a perennial herb belonging to the Labiate family and is widely distributed in the northeastern Asian countries such as Korea, Japan, and China. It is reported to display diverse biological activities including anti-microbial, anti-cancer, and anti-inflammation as determined by in vitro or in vivo studies. So far, about 200 compounds have been isolated from PV plant and a majority of these have been characterized mainly as triterpenoids, sterols and flavonoids, followed by coumarins, phenylpropanoids, polysaccharides and volatile oils. This review summarizes and analyzes the current knowledge on the chemical constituents, pharmacological activities, mechanisms of action and clinical applications of the PV plant including its potential as a future medicinal plant. Although some of the chemical constituents of the PV plant and their mechanisms of action have been investigated, the biological activities of many of these remain unknown and further clinical trials are required to further enhance its reputation as a medicinal plant.

Genetic diversity and its conservation implications of Vitex rotundifolia (Lamiaceae) populations in East Asia.

Vitex rotundifolia is an important coastal and medicinal plant, and is recorded in the List of the Important Wild Plants for Conservation in China and Japan. However, an effective conservation strategy is lacking. In the present study, the genetic diversity and population structure were analyzed using phylogeographical methods based on the trnH-psbA and trnG-trnS intergenic spacers of the chloroplast DNA (cpDNA) sequences from 157 individuals from 25 sampling sites for V. rotundifolia and V. trifolia plus the internal transcribed spacer (ITS) of the nuclear ribosomal DNA (nrDNA) sequences of 177 individuals from 27 sampling sites. The results showed that V. rotundifolia and V. trifolia had eight cpDNA and two nrDNA haplotypes, respectively, and the V. rotundifolia has a low level of genetic diversity (haplotype diversity h d,cp = 0.360, h d,nr = 0.440), a more pronounced genetic differentiation among populations (population differentiation at the species level (G ST) = 0.201, population differentiation at the allele level (N ST) = 0.462), and an insignificantly different phylogeographical structure (N ST > G ST, P > 0.05). In addition, haplotype network analyses indicated that V. rotundifolia and V. trifolia have distinct haplotypes. Divergence dating based on BEAST software analyses showed that most cpDNA clades diverged in the late Pleistocene era. Demographic analysis indicated that V. rotundifolia underwent a rapid demographic expansion. Some scientific strategies are suggested for resource conservation of V. rotundifolia based on its genetic diversity and population structure.

ErHuang Formula Improves Renal Fibrosis in Diabetic Nephropathy Rats by Inhibiting CXCL6/JAK/STAT3 Signaling Pathway.

Diabetic nephropathy (DN) is one of the main causes of renal fibrosis and is associated with high morbidity and mortality. Traditional Chinese Medicine (TCM) therapy has a long history of usage in a clinical setting and its usage is increasing. ErHuang Formula (EHF), a Chinese herbal compound, has been clinically used in treating DN for more than 30 years. However, its mechanism of action is still unknown. This study was conducted to evaluate the effect of EHF on renal fibrosis in a DN rat model and explore its underlying mechanism. The DN rat model was established by high-sugar-fat diet combined with a single intraperitoneal injection of streptozotocin (STZ), and EFH extract (4, 2, 1 g/kg d-1) was administered orally for 8 weeks. The biochemical parameters (blood glucose, weight, Scr, BUN, UA, U-Alb and UAE) were analyzed. The pathological changes in renal tissue were observed by histological staining with H&E and Masson. The effect of EHF on the proliferation of NRK-49F cells was examined by CCK-8 assay and the levels of several inflammation and fibrosis related cytokines (IL-6, TNF-α, TGF-ß1, Collagen I/III, MMP2/9) in serum and NRK-49F cell culture supernatants were detected by enzyme-linked immunoassay (ELISA). The mRNA levels of CXCL6, CXCR1, Collagen I/III, MMP2/9 in renal tissue were also measured by quantitative RT-PCR. Furthermore, the protein expression of PCNA, Collagen I/III, MMP2/9, CXCL6, CXCR1, p-STAT3, STAT3 in renal tissue and NRK-49F cells were determined by western blot. EHF improved the abnormal biochemical parameters and ameliorated the abnormal histology and fibrosis of renal tissue in a dose-dependent manner. EHF inhibited NRK-49F proliferation and decreased the expressions of inflammation and fibrosis related factors both in vitro and in vivo. Interestingly, the levels of Collagen I/III, PCNA, MMP2/9 and p-STAT3 were positively correlated with CXCL6. The amelioration of renal fibrosis in DN by EHF is related to CXCL6/JAK/STAT3 signal pathway, which is associated with inflammation and fibrosis of the tissue. These findings may have clinical implications for the treatment of DN.

New tetracyclic triterpenoids from Jatropha gossypiifolia induce cell-cycle arrest and apoptosis in RKO cells.

Four new tetracyclic-type triterpenoids, jatrogossols A - D (1-4), along with 5 known analogues (5-9), were isolated from the ethanol extract of the branches and leaves of Jatropha gossypiifolia. The absolute configurations of 1-4 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicities of the triterpenoids were evaluated using RKO and HepG2 human cancer cell lines. Compound 8 was cytotoxic against RKO colon cancer cells with an IC50 value of 12.5 µM. The morphological features of apoptosis were evaluated in 8-treated RKO cells. Compound 8 effectively induced apoptosis of RKO, which was associated with G1 or S phase cell cycle arrest. Flow cytometric analysis showed that treatment with 8 significantly induced RKO cell apoptosis in a dose-dependent manner.

Chemical Constituents and Pharmacological Activities of Stellera chamaejasme.

BACKGROUND: Stellera chamaejasme is a perennial weed and is found across a wide geographic range. It is found in the Altai of eastern Russia, northern China and Mongolia southwards and reaches as far as the western Himalayas of the Qinghai-Tibet and Yungui Plateaus. The dried roots of S. Chamaejasme are named "Rui- Xiang-Lang-Du" and this herb with toxic properties is widely used in Traditional Chinese Medicine for the treatment of various disorders. It is effective against dispelling phlegm by water and displays toxicity against insect pests. This review provides a comprehensive overview of the chemical composition and the pharmacological properties of S. Chamaejasme thus providing a better insight into its application in the prevention of human disease. METHODS: A comprehensive literature review was undertaken and the main chemical compounds found in S. Chamaejasme were identified on the basis of their chemical formula and structure. These included flavonoids, coumarins, lignans, diterpenoids plus others, and their pharmacological properties were also summarized in detail. RESULTS: The main constituents of S. Chamaejasme included flavonoids, coumarins, lignans, diterpenoids plus other compounds. The pharmacological properties of these compounds displayed a wide spectrum and include anti-tumors, anti-viral, anti-bacterial, anti-convulsive, anti-epileptic, insecticide, anti-inflammation, regulation of immunity etc. The diterpenoids were widely recognized as the constituent responsible for the anti-tumor effect. CONCLUSION: A large number of studies conclude that S. Chamaejasme displays a wide spectrum of pharmacological activity with the anti-tumor activity being significant.

Antitumor Activity of Diterpenoids from Jatropha gossypiifolia: Cell Cycle Arrest and Apoptosis-Inducing Activity in RKO Colon Cancer Cells.

Nine new minor diterpenoids, jatrogossones A-I (1-9), and six known analogues (10-15) were separated from an extract of the branches and leaves of Jatropha gosspiifolia. Compounds 4-6 and 10, possessing a 5/11 fused-ring skeleton, and 8, 9, and 13, with a 5/9/5 fused-ring skeleton, represent rare diterpenoid skeletons that have been found only in compounds isolated from plants of the Jatropha genus. The absolute configurations of 1-10 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicity of the diterpenoids was evaluated using RKO and LOVO colon cancer cells in which regenerating islet-derived protein 3-alpha (Reg3A) is highly expressed. Compound 12 exhibited cytotoxicity against RKO colon cancer cells with an IC50 value of 2.6 µM. Morphological features of apoptosis and antimigration activities were evaluated in 12-treated RKO cells. Compound 12 effectively induced apoptosis of RKO, which was associated with G2/M-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 12 significantly induced RKO cell apoptosis in a dose-dependent manner.

Chinese Herbal Formulas and Renal Fibrosis: An Overview.

All forms of chronic kidney disease (CKD) eventually lead to renal fibrosis irrespective of its origin. It is generally characterized by an excessive accumulation and deposition of extracellular matrix (ECM) and to date, no ideal treatment has been established. Bian-Zheng-Lun-Zhi (syndrome differentiation and treatment), a classic feature of traditional Chinese Medicine (TCM), is a unique method used to diagnose and treat the pathology of a disease. Zheng (syndrome) is used to demonstrate the nature of a disease completely in an extensive and specific manner. Chinese herbal formulas are determined according to TCM theory and this review highlights these formulas and suggests a possible mechanism for their use in the treatment of renal fibrosis.