Research Progress in Traditional Applications, Phytochemistry, Pharmacology, and Safety Evaluation of Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR) belongs to the family Cynomoriaceae. It is a perennial succulent parasitic herb with a reddish-brown coloration, predominantly submerged in sand and lacking chlorophyll. Traditionally, it has been used in ethnic medicine to treat various diseases, such as gastric ulcers, indigestion, bowel movements, and improving sexual function. To comprehensively collect CSR data, extensive literature searches were conducted using medical, ecological, and scientific databases such as Google Scholar, PubMed, Science Direct, Web of Science, and China National Knowledge Infrastructure (CNKI). This article summarizes and categorizes research on the uses, phytochemical characteristics, pharmacological activities, and toxicity of ethnic medicine, with the aim of establishing a solid foundation and proposing new avenues for exploring and developing potential applications of CSR. So far, a total of 98 compounds have been isolated and identified from CSR, including flavonoids, terpenes, steroids, and other compounds. It is worth noting that flavonoids and polysaccharides have significant antioxidant and anti-inflammatory properties. In addition, these compounds also show good application prospects in anti-tumor, antioxidant, anti-aging, anti-fatigue, anti-diabetes, and other aspects. Although extensive progress has been made in the basic research of CSR, further research is still needed to enhance the understanding of its mechanism of action and explore more unknown compounds. Our review indicates that CSR has broad prospects and deserves further research.

Taraxacum: A Review of Ethnopharmacology, Phytochemistry and Pharmacological Activity.

Taraxacum refers to the genus Taraxacum, which has a long history of use as a medicinal plant and is widely distributed around the world. There are over 2500 species in the genus Taraxacum recorded as medicinal plants in China, Central Asia, Europe, and the Americas. It has traditionally been used for detoxification, diuresis, liver protection, the treatment of various inflammations, antimicrobial properties, and so on. We used the most typically reported Taraxacum officinale as an example and assembled its chemical makeup, including sesquiterpene, triterpene, steroids, flavone, sugar and its derivatives, phenolic acids, fatty acids, and other compounds, which are also the material basis for its pharmacological effects. Pharmacological investigations have revealed that Taraxacum crude extracts and chemical compounds contain antimicrobial infection, anti-inflammatory, antitumor, anti-oxidative, liver protective, and blood sugar and blood lipid management properties. These findings adequately confirm the previously described traditional uses and aid in explaining its therapeutic applications.

Anthocyanins from Lycium ruthenicum Murray Inhibit HepG2 Cells Growth, Metastasis and Promote Apoptosis and G2/M Phase Cycle Arrest by Activating the AMPK/mTOR Autophagy Pathway.

Among the most common malignancies in humans, liver cancer ranks third in terms of mortality in the world. Seeking new anticancer drugs or adjuvant chemotherapy drugs from natural products has attracted the attention of many researchers. Lycium ruthenicum Murray (LR), a health food and traditional Chinese medicine, exerts extensive pharmacological properties, of which anthocyanins are one of the key active components. In this research, we explored the antitumor activity and autophagy regulation mechanism of anthocyanins from Lycium ruthenicum Murray (ALR) in HepG2 cells. Our results found that ALR profoundly reduced the cell viability, clone formation, migration, and invasion and promoted apoptosis and G2/M phase arrest of HepG2 cells in a dose-dependent pattern. Further studies confirmed that ALR treatment significantly increased the number of autophagic vacuoles and autophagosomes, upregulated the expression of Beclin-1, p62, LC3-II/LC3-I, and p-AMPK, and concomitantly downregulated the expression of p-mTOR. When autophagy was inhibited by 3-methyladenine (3-MA), ALR-induced proliferation inhibition, invasion, and migration capabilities, as well as apoptosis rate and G2/M phase arrest, were all reversed, and the activities of key proteins in the AMPK/mTOR pathway were all constrained. In summary, the results presented here indicate that ALR may be effective as a natural antitumor agent by activating AMPK and inhibiting the mTOR autophagy pathway in HepG2 cells.

The analgesic activities of total alkaloids of the ethnic medicine Cynanchum komarovii Al. Iljinski.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum komarovii Al. Iljinski is a ethnomedicinal herb and this ethno-medicine is used mainly to treat arthritis, toothache, reducing phlegm, relieving cough. Total alkaloids of Cynanchum komarovii Al. Iljinski (TACKI) is the main active compound of Cynanchum komarovii Al. Iljinski. Previous investigations have revealed that TACKI can significantly inhibit rat foot swelling caused by carrageenan; it has a significant inhibitory effect on granulation tissue proliferation. Pharmacology study showed that Cynanchum komarovii Al. Iljinski has analgesia, anti-inflammatory, antibacterial, anti-tumor, relieving cough and relieving asthma. However, there is no any investigation on the mechanism of analgesia and anti-inflammation. AIM OF THE STUDY: To clarify the analgesic effect and material basis of Cynanchum komarovii Al. Iljinski, determine the analgesic effect of TACKI, and provide experimental data support for its traditional application in the treatment of various pains. MATERIALS AND METHODS: TACKI were prepared by the traditional acid extraction and alkaline precipitation method, and TACKI was analyzed through classic animal models of acute antinociceptive animal models and chronic antinociceptive. Evaluation of analgesic effects, and preliminary discussion of the mechanism of its analgesic effects were performed in this work. RESULTS: Acute toxicity experiments showed that the LD50 of TACKI mice was 2960.88 mg/kg, and symptoms of poisoning appeared. Patholog of liver and kidney studies have shown that TACKI reduces eosinophils and increases basophils in kidney glomeruli. In the study of analgesic effects, TACKI had analgesic activity through the PWL, formalin test, and acetic acid writhing test. In the chronic inflammatory antinociceptive study, the latency of the withdrawal reflex in the TACKI group was prolonged, and the mechanical withdrawal reflex threshold was significantly increased. The protein expression of NMDA, GFAP and Iba-1 in rat brain tissue can be reduced significantly byTACKI. Meanwhile, the content of TNF-α and IL-6 in rat brain tissue is reduced. CONCLUSION: TACKI has a significant analgesic activities. It may be related to inhibiting the activation of astrocytes and reducing the content of inflammatory mediators.

Circ_0001658 regulates gefitinib resistance of non-small cell lung cancer through miR-409-3p/TWIST1 axis.

To investigate the function and mechanism of circular RNA circ_0001658 on gefitinib resistance of non-small cell lung cancer (NSCLC) cells. Circ_0001658, microRNA (miRNA, miR)-409-3p and twist family bHLH transcription factor 1 (TWIST1) expression levels in NSCLC tissues and cell lines were probed by quantitative real-time PCR and Western blot assays. Cell counting kit-8 assay was adopted to examine the inhibitory effect of different concentrations of gefitinib on the viability of NSCLC cells, with the 50% concentration of inhibition (IC50) value calculated. Besides, BrdU assay and flow cytometry assay were used to detect the proliferative and apoptotic rate of NSCLC cells. What's more, the binding relationships between miR-409-3p and circ_0001658, miR-409-3p and TWIST1 mRNA 3' untranslated region (3' UTR) were confirmed by dual-luciferase reporter gene assay and RNA immunoprecipitation assay. Circ_0001658 expression was raised in NSCLC tissue samples and cell lines, which was significantly associated with TNM stage and the differentiation degree of NSCLC tissues. Knocking down circ_0001658 could restrain the viability of NSCLC cells, promote the apoptosis, and reduce the IC50 of gefitinib, while transfection of miR-409-3p inhibitors could partially reverse these impacts. Additionally, circ_0001658 directly targeted miR-409-3p and negatively modulated its expression. TWIST1 was the target of miR-409-3p, which could be indirectly and positively modulated by circ_0001658. Moreover, circ_0001658 expression was negatively interrelated with miR-409-3p expression, while positively correlated with TWIST1 expression in NSCLC samples. Circ_0001658 promotes the malignant phenotypes and the resistance to gefitinib of NSCLC cells by regulating the miR-409-3p/TWIST1 axis.

Synergistic Effect of Baculovirus-Mediated Endostatin and Angiostatin Combined with Gemcitabine in Hepatocellular Carcinoma.

Anti-angiogenic gene therapy is a promising strategy in treating cancer. Endostatin and angiostatin are widely used in tumor anti-angiogenesis therapy. Our previous studies have shown that the BDS-hEA, a baculovirus long-term expressing the fusion protein of human endostatin and angiostatin, has a favorable effect in inhibiting the growth and angiogenesis of hepatocellular carcinoma. The purpose of this study was to further investigate its synergistic antitumor efficiency in combination with low-dose chemotherapeutic gemcitabine (GEM) on the subcutaneous hepatocellular carcinoma xenograft model in nude mice. The results showed that the combined group significantly inhibited (p < 0.05 or p < 0.01 or p < 0.001) the growth of tumor weight and volume, reduced the expression of ki67 (cell proliferation marker), CD31 (angiogenic marker) and Matrix metalloproteinase 9 (MMP-9, tumor invasion and metastasis marker) and increased the apoptosis of tumor cells compared with the monotherapy and control groups, respectively. Synergistic index results showed that BDS-hEA combined with GEM had a synergistic effect in inhibiting tumor volume, proliferation, microvessel density, metastasis and promoting tumor apoptosis. Furthermore, there were no metastatic nodules and obvious pathological changes in liver tissue of the combined group, and the serum liver function indicators aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-BIL), alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) were significantly reduced (p < 0.05 or p < 0.01 or p < 0.001) in the BDS-hEA or GEM groups compared with the control group. Notably, the combined therapy showed lower levels of liver function indicators than the GEM group. These data support the view that the combination of BDS-hEA and GEM has a synergistic anti-tumor properties and can reduce the damage of liver to certain extent.

Taraxacum mongolicum extract inhibited malignant phenotype of triple-negative breast cancer cells in tumor-associated macrophages microenvironment through suppressing IL-10 / STAT3 / PD-L1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Triple-negative breast cancer (TNBC) is the most aggressive and the worst prognosis breast cancer with limited treatment options. Taraxacum mongolicum (also called dandelion) is a traditional Chinese medicine has been used to treat mastitis, breast abscess, and hyperplasia of mammary glands since ancient times. In modern pharmacological research, dandelion has been proven with anti-breast cancer activities. We previously reported that dandelion extract could induce apoptosis in TNBC cells. However, its anti-tumor effects and mechanisms in the tumor microenvironment have not yet been elucidated. AIM OF THE STUDY: Tumor-associated macrophages (TAMs) play an important role in regulating the interaction between tumor cells and the immune system. The present study aimed to investigate the effects and mechanisms of dandelion extract on TNBC cells under the microenvironment of TAMs, as well as its influence on the polarization of M2 macrophages. MATERIALS AND METHODS: M2 macrophages were induced by phorbol-12-myristate 13-acetate (PMA) and interleukin 4 (IL-4), and verified by flow cytometry, quantitative RT-PCR (qRT-PCR), Western blotting, and ELISA. MDA-MB-231 and MDA-MB-468 TNBC cells were co-cultured with the supernatant of M2 macrophage which providing the TAMs microenvironment. The antitumor activity of dandelion extract in TNBC cells was evaluated by MTT assay. The invasive and migratory capacity of TNBC cells was measured by transwell assays. The expression of protein and gene was assessed by Western blotting and qRT-PCR, respectively. RESULTS: TAMs microenvironment promoted the proliferation, migration, and invasion of TNBC cells. However, dandelion extract inhibited the malignant property of MDA-MB-231 and MDA-MB-468 cells induced by TAMs. Both of TAMs and IL-10 caused STAT3 activation and PD-L1 higher expression, the immunosuppressive molecules in TNBC cells, and this effect can be attenuated by IL-10 neutralizing antibody. Dandelion extract exerted inhibition on STAT3 and PD-L1 in TNBC cells under TAMs microenvironment. Furthermore, in M2 macrophages, dandelion extract remarkably promoted the expression of M1-like marker TNF-α, IL-8, and iNOS, but reduced M2-like marker IL-10, CD206, Arginase-1, and TGF-ß. CONCLUSION: Dandelion extract inhibited the proliferation, migration and invasion of TNBC cells in TAMs microenvironment through suppressing IL-10/STAT3/PD-L1 immunosuppressive signaling pathway. Furthermore, dandelion extract promoted the polarization of macrophages from M2 to M1 phenotype. Thus, our results indicated that dandelion may serve as a promising therapeutic strategy for TNBC by modulating tumor immune microenvironment.

A comprehensive automatic data analysis strategy for gas chromatography-mass spectrometry based untargeted metabolomics.

Automatic data analysis for gas chromatography-mass spectrometry (GC-MS) is a challenging task in untargeted metabolomics. In this work, we provide a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (autoGCMSDataAnal) by developing a new automatic strategy for performing TIC peak detection and resolution and proposing a novel time-shift correction and component registration algorithm. autoGCMSDataAnal uses original acquired GC-MS datafiles as input to automatically perform TIC peak detection, component resolution, time-shift correction and component registration, statistical analysis, and compound identification. We utilize standards and complex plant samples to comprehensively investigate the performance of autoGCMSDataAnal. The results suggest that the developed strategy is comparable with several state-of-the-art methods that are widely used in GC-MS-based untargeted metabolomics. Based on the proposed strategy, we develop a user-friendly MATLAB GUI for users who are unfamiliar with programming languages to facilitate their routine analysis, which can be freely downloaded at: http://software.tobaccodb.org/software/autogcmsdataanal.

Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides L., which is called Kudouzi in China, is a medicinal plant distributed in Western and Central Asia, especially in China, and has been used for decades to treat fever, bacterial infection, heart disease, rheumatism, and gastrointestinal diseases. AIM OF THE REVIEW: This review aims to provide up-to-date information on S. alopecuroides, including its botanical characterization, medicinal resources, traditional uses, phytochemistry, pharmacological research, and toxicology, in exploring future therapeutic and scientific potentials. MATERIALS AND METHODS: The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, PhD and MS dissertations, and other web sources, such as the official website of Flora of China and Yao Zhi website (https://db.yaozh.com/). RESULTS: A total of 128 compounds, such as alkaloids, flavonoids, steroids, and polysaccharides, were isolated from S. alopecuroides. Among these compounds, the effects of alkaloids, such as matrine and oxymatrine, were extensively studied and developed into new drugs. S. alopecuroides and its active components had a wide range of pharmacological activities, such as anticancer, antiviral, anti-inflammatory, antimicrobial, analgesic, and neuroprotective functions, as well as protective properties against pulmonary fibrosis and cardiac fibroblast proliferation. CONCLUSIONS: As an important traditional Chinese medicine, modern pharmacological studies have demonstrated that S. alopecuroides has prominent bioactivities, especially on gynecological inflammation and hepatitis B, and anticancer activities. These activities provide prospects for novel drug development for cancer and some chronic diseases. Nevertheless, the comprehensive evaluation, quality control, understanding of the multitarget network pharmacology, long-term in vivo toxicity, and clinical efficacy of S. alopecuroides require further detailed research.

Automatic peak detection coupled with multivariate curve resolution-alternating least squares for peak resolution in gas chromatography-mass spectrometry.

Gas chromatography-mass spectrometry (GCMS) has been extensively used in complex sample analysis for the high-throughput characterization of volatile and semivolatile compounds. However, the accurate extraction of compound information remains challenging. Here, we present a combined algorithm strategy for GCMS data analysis to accurately screen metabolites across groups. First, chromatographic peaks in a total ion chromatogram (TIC) are extracted by using a Gaussian smoothing strategy and aligned on the basis of their mass spectra by a dynamic programing algorithm. The aligned TIC peaks are then registered into a component list table by applying a nearest-neighbor clustering algorithm. Significantly expressed TIC peaks among groups are screened through statistical analysis, such as ANOVA. Second, a chemometric method of multivariate curve resolution-alternating least squares for the peak resolution of the screened TIC peaks is utilized to retrieve the chromatographic and mass spectral profiles of coeluted components. The developed strategy is employed for the analysis of standard and complex plant sample datasets. Results indicate that our methodology is comparable with several state-of-the-art methods that are widely used in GC-MS-based metabolomics.

Ethnobotany, Phytochemistry and Pharmacological Effects of Plants in Genus Cynanchum Linn. (Asclepiadaceae).

Genus Cynanchum L. belongs to the family Asclepiadaceae, which comprise more than 200 species distributed worldwide. In Chinese medical practice, numerous drugs (such as tablets and powders) containing different parts of plants of this genus are used to treat snake bites, bruises, osteoblasts, rheumatoid arthritis and tumors. A search for original articles published on the cynanchum genus was performed by using several resources, including Flora of China Official Website and various scientific databases, such as PubMed, SciFinder, the Web of Science, Science Direct, and China Knowledge Resource Integrated (CNKI). Advances in the botanical, ethnomedicinal, phytochemical, and pharmacological studies of this genus are reviewed in this paper. Results showed that more than 440 compounds, including C21 steroids, steroidal saponins, alkaloids, flavonoids and terpene, have been isolated and identified from Cynanchum plants up to now. In vivo and in vitro studies have shown that plants possess an array of biological activities, including anti-tumor, neuroprotective and anti-fungal effects. Popular traditional prescription of Cynanchum sp. was also summed up in this paper. However, many Cynanchum species have received little or no attention. Moreover, few reports on the clinical use and toxic effects of Cynanchum sp. are available. Further attention should be focused on the study of these species to gather information on their respective toxicology data and relevant quality-control measures and clinical value of the crude extracts, active compounds, and bioactive metabolites from this genus. Further research on Cynanchum sp. should be conducted, and bioactivity-guided isolation strategies should be emphasized. In addition, systematic studies of the chemical composition of plants should be enhanced.

Two new 18, 19-seco Triterpenoids from Ilex asprella (Hook. et Arn.) Champ. ex Benth.

Two novel 18,19-seco-ursane triterpenoid saponins, ilexasprellanosides J-K (1-2, resp.), 3-O-α-l-Rhamnopyranosyl-(1 → 2)-ß-d-xylopyrannosyl-19-O-ß-d-glucopyranosyl-16-ß-hydroxyl-18,19-seco-13(18)-urs-ene-21, 28-lactone (1), 3-O-ß-d-Xylopyrannosyl-19-O-α-l-rhamnopyran osyl-(1 → 2)-α-l-arabinopyranoside-16, 21-epoxy-18, 19-seco-13(18)-urs-ene-28-oic acid (2), five known compounds (3-7) were isolated from the leaves of Ilex asprella (Hook. et Arn.) Champ. ex Benth. (Gangmeiye). The chemical structures of these compounds were elucidated through UV, IR, ESI-MS, 1H NMR and 13C NMR analyses. In MTT and SRB assays, compounds 1-4 presented cytotoxic activities against several human cancer cell lines, namely, the HL-60 human acute promyelocytic leukaemia, Bel 7402 liver cancer, BGC-823 gastric cancer and KB human nasopharyngeal carcinoma cell lines. Compound 1 exhibited weak cytotoxic activities against the human tumour cell lines HL-60, Bel 7402 and KB with inhibition rates of 27.97%, 21.00% and 25.60%, respectively. Compound 2 exhibited weak cytotoxic activities against the human tumour cell lines HL-60, Bel 7402 and BGC-823 with inhibition rates of 19.34%, 7.50% and 4.26%. Respectively, the compounds exerted no statistically different effects on mast cell degranulation in rats. This result indicates that the compounds do not affect mast cell degranulation.

Anti-Proliferative Effect of Triterpenoidal Glycosides from the Roots of Anemone vitifolia through a Pro-Apoptotic Way.

A cytotoxicity-guided phytochemical investigation of Anemone vitifolia roots led to the isolation of six oleanane saponins (1-6), which were reported from the species for the first time. Their structures were determined by comparing its MS and NMR data with those in literature. Compounds 1-4 showed significant inhibitory effects on the proliferation of hepatocellular carcinoma HepG2 cells with IC50 values ranging from 2.0 to 8.5 µM, compared to positive control methotrexate with IC50 value of 15.8 µM. Flow cytometry analysis revealed that compounds 1-4 exerted anti-proliferative effects through a pro-apoptotic way of hepatocellular carcinoma cells.

[Advances on chemical constituents and bioactivities of genus Stellera].

Advance on chemical constituents and pharmacological activities of Stellera plants have been conducted. The chemical constituents include terpenes, coumarins, flavonoids, lignans, volatile oils, and other compounds. Pharmacological studies showed that diterpenoids and biflavones showed strong activities, such as antitumor, anti-HIV, and immune regulations. This review hopes to provide a scientific basis for further research and explorations of the medicinal values of the genus.

[Most advance on chemical and biological investigations of gorgonian-octocorals].

This review presents the most recent chemical and biological investigations on one of the marine invertebrates, gorgonian octocoral. It summarizes all 432 new compounds published in 2002-2009, which consists of 46 sesquiterpenoids (including 2 new natural products, NNP), 282 diterpenoids (including 4 from Pennatulacea octocoral and one artifact), 76 steroids, and 29 alkaloids or other types (2 NNP included). In this paper, according to the structure division, the new compounds are described in combination with the taxonomy of the investigated animals, and its simultaneous bioactivity results. Novel skeletons and complex structures are paid most emphasis on its features, means of structural elucidation and the proposed biogenesis pathway. The source of all new compounds and the different diterpenoid skeleton types are all listed and analyzed, as well as the commonly used Chinese names or some proposed ones for diterpenoid skeletons. Furthermore, this papers deals with all biological test toward the gorgonian new metabolites, i.e. anti-cancer, anti-inflammatory, anti-bacterial(against Staphylococcus aureus bacteria, Mycobacterium tuberculosis etc), anti-malaria, and anti-fouling as well, in which anti-cancer activity and cytotoxicity were additionally, a discussion and prospect are proposed regarding chemical overview on gorgonian. This review, hopefully, can be useful in proving data and references for further chemical and biological research of China sea gorgonian, for the studies on chemical ecology, and for the discovery of new and bioactive compounds or the marine-derived leading targets.

Three new acylated glycosides from the stems of Casearia velutina and their protective effect against H2O2-induced impairment in PC12 cells.

Chemical investigation of the stems of Casearia velutina led to the isolation and structural elucidation of three new acylated glycosides, casearicosides A-C (1-3), together with 13 known compounds. The structures of the new compounds were established by spectroscopic and chemical methods. These isolates were evaluated for protective effects against H(2)O(2)-induced impairment in PC12 cells and inhibitory activity against snake venom phosphodiesterase I. A brief chemotaxonomy of the genus Casearia is also discussed.