Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans.

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.

Isolation and target identification of anti-renal fibrosis compounds from Cordyceps militaris.

Four undescribed compounds including one aromatic glucoside derivative, cordyceglycoside A (1), one new isoleucine derivative inner salt, cordycepisosalt A (2), a rare four-membered lactam, cinerealactam B (3), and one sesquiterpene derivative, cordycepsetp A (4), together with six known compounds were isolated from Cordyceps militaris. The structures including absolute configurations of these new compounds, were unambiguously elucidated by spectroscopic data analysis and single crystal X-ray diffraction. Biological evaluation of compounds 1-4 showed that 3 displays anti-renal fibrotic activities in TGF-ß1 induced NRK-52e cells. Furthermore, DARTS coupled with LC-MS/MS analysis was used to identify candidate target proteins for 3. Subsequently, C1qbp knockdown using siRNA allowed us to validate the target protein of 3.

Serum Pharmacochemistry Combined with Network Pharmacology-Based Mechanism Prediction and Pharmacological Validation of Zhenwu Decoction on Alleviating Isoprenaline-Induced Heart Failure Injury in Rats.

Zhenwu decoction (ZWD) is a famous classical formula in the treatment of heart failure (HF) with significant clinical effects. Owing to the complex material basis of ZWD, it is challenging to elucidate the pharmacodynamic substances and pharmacological mechanisms of ZWD against HF. Therefore, an ultrahigh-performance liquid chromatography system coupled with a high-resolution orbitrap mass spectrometry method was used to profile the chemical components and the absorbed prototype constituents in ISO-induced HF rat serum after oral administration of ZWD, and 33 out of 115 compounds were identified. In the in vivo study, ZWD could improve cardiac function and reduce the content of serum biochemical indexes, which are heart failure markers. With the help of network pharmacology and molecular docking simulation analysis, 112 ZWD targets oriented by HF were obtained, with STAT3, TNF, AKT1, VEGFA, and ALB as the core targets. Furthermore, we found that paeoniflorin and its derivatives may play a bigger role than other serum migrant components. Enriched pathway analysis yielded multiple HF-related signaling pathways, which indicated that ZWD may attenuate HF through the effect of PI3K-Akt, and MAPK pathways by regulating key targets such as STAT3, TNF, and AKT1. Finally, STAT3/MAPK pathways were experimentally validated in the anti-HF effect of ZWD. The phosphorylation levels of p38, JNK, ERK, and STAT3 were significantly increased in the ISO group and reversed by ZWD intervention. The results provided a reasonable strategy for the rapid screening of bioactive components in ZWD and a reference for quality control and further mechanism study of ZWD.

Eight new 2-(2-phenylethyl)chromone derivatives from agarwood of Aquilaria sinensis with anti-inflammatory activity.

Eight previously unknown 2-(2-phenylethyl)chromone derivatives, called aquichromones A - E (1-3, 5 and 6) and 8-epi-aquichromone C (4), including two pairs of enantiomers [(±)-1 and (±)-2] were isolated from the agarwood of Aquilaria sinensis. The structures and absolute stereochemistry of these natural products were elucidated by using spectroscopic and computational methods. The result of biological assay showed that two members of this group, 4 and 5, have significant dose-dependent anti-inflammatory activity.

Retro-dihydrochalcones from the resin of Daemonorops draco and their inhibitory activities against renal fibrosis.

Daedracoflavan A-E (1-5), five new flavonoids were isolated from the resin of Daemonorops draco. Their structures including absolute configurations were established by using spectroscopic and computational methods. All the compounds are new chalcones with the same retro-dihydrochalcone skeleton. Compound 1 features the presence of a cyclohexadienone unit originating from a benzene ring, and the ketone group of C-9 reduced to a hydroxyl group. The bioactivity of all isolated compounds was evaluated in kidney fibrosis and found that compound 2 could dose-dependently inhibit the expression of fibronectin, collagen I, and α-SMA in TGF-ß1-induced rat kidney proximal tubular cells (NRK-52E). Interestingly, the replacement of a proton by a hydroxyl group at C-4' seems to play a crucial role in anti-renal fibrosis activity.

Crataegus pinnatifida: A botanical, ethnopharmacological, phytochemical, and pharmacological overview.

ETHNOPHARMACOLOGICAL RELEVANCE: Crataegus pinnatifida belongs to the Rosaceae family and extensively distribute in North China, Europe, and North America. Its usage was first described in "Xinxiu Ben Cao." The dried fruits of Crataegus pinnatifida Bunge or Crataegus pinnatifida var. major N. E. Br., also known as "Shanzha," is a famous medicine and food homology herb with a long history of medicinal usage in China. C. pinnatifida has the functions for digestive promotion, cardiovascular protection, and lipid reduction. It was traditionally used to treat indigestion, cardiodynia, thoracalgia, hernia, postpartum blood stagnation, and hemafecia. In recent years, C. pinnatifida has attracted worldwide attention as an important medicinal and economical crop due to its multiple and excellent health-promoting effects on cardiovascular, nervous, digestive, endocrine systems, and morbigenous microorganisms of the human body due to its medicinal and nutritional values. AIM OF THE REVIEW: The current review aims to provide a comprehensive analysis of the geographical distribution, traditional usage, phytochemical components, pharmacological actions, clinical settings, and toxicities of C. pinnatifida. Moreover, the connection between the claimed biological activities and the traditional usage, along with the future perspectives for ongoing research on this plant, were also critically summarized. MATERIALS AND METHODS: We collected the published literature on C. pinnatifida using a variety of scientific databases, including Web of Science, ScienceDirect, PubMed, Wiley, Springer, Taylor & Francis, ACS Publications, Google Scholar, Baidu Scholar, CNKI, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations) from 2012 to 2022. RESULTS: In the last decade, over 250 phytochemical compounds containing lignans, phenylpropanoids, flavonoids, triterpenoids, and their glycosides, as well as other compounds, have been isolated and characterized from different parts, including the fruit, leaves, and seeds of C. pinnatifida. Among these compounds, flavonoids and triterpenoids were major bioactive components of C. pinnatifida. They exhibited a broad spectrum of pharmacological actions with low toxicity in vitro and in vivo, such as cardiovascular protection, neuroprotection, anti-inflammatory, antioxidant, antibacterial, antiviral, anti-diabetes, anti-cancer, anti-mutagenic, anti-osteoporosis, anti-aging, anti-obesity, and hepatoprotection and other actions. CONCLUSION: A long history of traditional uses and abundant pharmacochemical and pharmacological investigations have demonstrated that C. pinnatifida is an important medicine and food homology herb, which displays outstanding therapeutic potential, especially in the digestive system and cardiovascular disease. Nevertheless, the current studies on the active ingredients or crude extracts of C. pinnatifida and the possible mechanism of action are unclear. More evidence-based scientific studies are required to verify the traditional uses of C. pinnatifida. Furthermore, more efforts must be paid to selecting index components for quality control research and toxicity and safety studies of C. pinnatifida.

A review of the genus Chrysosplenium as a traditional Tibetan medicine and its preparations.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of genus Chrysosplenium have a long history of application and are distributed in many countries, especially in Tibetan regions of China. The genus has been used locally in the treatment of various hepatobiliary diseases such as "Chiba disease" (related to cholecystitis, cholelithiasis, acute icteric hepatitis, and acute liver necrosis in modern medicine). AIM OF THE REVIEW: This review summarizes and critically analyzes the aspects of the botanical morphology and distribution, traditional uses, phytochemistry, pharmacological activities, quality control, and development status of preparations of the genus Chrysosplenium. Moreover, the future research direction and focus of the genus are also discussed. We hope to provide a valuable reference for researchers who are interested in the genus Chrysosplenium. MATERIALS AND METHODS: The relevant information of the genus Chrysosplenium was gathered through electronic databases from 1968 to 2021, including PubMed, Web of Science, ScienceDirect, Google Scholar, Springer, CNKI, and Wan Fang, as well as PhD, MSc thesis, Chinese Pharmacopoeia (2020 edition), Tibetan medicine monographs. In addition, plant names were verified by "The Plant List" (The Plant List Database, http://www.theplantlist.org). RESULTS: Based on existing studies of chemical compositions, more than 90 compounds have been identified from Chrysosplenium species, including flavonoids, triterpenoids, volatile oils, steroids, alkaloids, and other compounds. The highly hydroxylated and methoxylated flavonoids and triterpenoids are the main active components. In addition, many studies have shown that the extracts and some components isolated from the genus Chrysosplenium have a variety of pharmacological activities, such as anti-tumor, antibacterial, anti-viral, hepatoprotective, and insecticidal properties. Furthermore, there are only 9 preparations with Chrysosplenium species as one of the medicinal materials. Among these preparations, C. nudicaule is used more and other Chrysosplenium species are rarely involved. CONCLUSIONS: Most medicinal species of Chrysosplenium have not only good therapeutic effects in traditional uses, but also a great potential for development in modern pharmaceutical studies. However, the material basis and mechanism of action of this genus have not been well explained. Therefore, further systematic and comprehensive research on the genus Chrysosplenium is still required to provide a scientific basis for its clinical applications.