New Monoterpenoid Indole Hybrids from Gelsemium elegans with Anti-Inflammatory and Osteoclast Inhibitory Activities.

Gelsegansymines A (1) and B (2), two new indole alkaloids along with six known analogues (3-8) were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques. Structurally, compounds 1 and 2 possessed the rare cage-like gelsedine skeleton hybrid with bicyclic monoterpenoid. The anti-inflammatory activities of isolated compounds (1-3) were tested on LPS induced RAW264.7 cells. Under the treated concentration without toxicity for cells, the cytokines levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated by Griess method and enzyme-linked immunosorbent assay (ELISA). The results showed that compounds 1-3 exhibited anti-inflammatory activities with dose-dependent manner range from 12.5 to 50 µmol/L. Furthermore, the inhibitory activities of compounds 1 and 2 on receptor activator of NF-κB ligand (RANKL) induced osteoclast formation were tested in vitro. Compounds 1 and 2 at 5 µmol/L exhibited the significant inhibitory effect on the osteoclastogenesis induced by RANKL. This work reported the anti-inflammatory and osteoclast inhibitory activities of new monoterpenoid indole hybrids, which may inspire the further light on the related traditional application research of G. elegans.

Genus Gelsemium and its Endophytic Fungi - Comprehensive Review of their Traditional Uses, Phytochemistry, Pharmacology, and Toxicology.

BACKGROUND: The use of ethnic medicinal plants has revitalized wide popularity in Africa, Asia, and most of the world because of the energy consumption barriers increase of synthetic drugs. Gelsemium is a traditional genus of plants with famous cultural and medicinal significance in Southeast Asia and North America. Three species are reported from the genus Gelsemium, including Gelsemium elegans (Gardn. & Camp.) Benth., Gelsemium sempervirens (L.) J.St.-Hil., and Gelsemium rankinii Small. Among them, G. elegans is well known for its toxicity and is used as a traditional remedy for skin problems, neuralgia, fractures, and cancer. The first record of the toxic medicine G. elegans is the Chinese herbal medicine classically known as Shen-Nong Ben-Cao Jing. In the legend, the Shennong emperor was poisoned by G. elegans, hence, it is also wellknown as Duan Chang Cao in China. In addition, G. sempervirens tincture is also used in the treatment of inflammation of the spinalcolumn, and diminishes blood to the cerebrospinal centers. INTRODUCTION: This review aims to provide up-to-date information on Gelsemium and its endophytic fungi on their traditional uses, phytochemistry, pharmacology, and toxicology. Mechanism studies regarding the detoxification profile of Gelsemium are also reviewed. METHODS: For this updated review, the literature survey and search were performed on the scientific databases PubMed, ScienceDirect, Wiley, China CNKI, Web of Science, SciFinder, and Google Scholar using the relevant keywords. RESULTS: The plants of the genus Gelsemium are all reported as rich sources of monoterpene indole alkaloids. Previous phytochemical studies published more than 200 alkaloids from Gelsemium and its endophytic fungi, which have attracted considerable attention from pharmaceutists and phytochemists due to their diverse and complex structures. The bioactivities of Gelsemium phytoconstituents studied using various chemical methods are summarized and described herein. Considering the huge influence of Gelsemium regarding its traditional applications, the activities of isolated compounds were focused on the anti-tumor, anti-inflammatory, analgesic and antianxiety, immunostimulatory, and immunosuppressive properties, which provide evidence supporting the ethnopharmacological effectiveness of the genus Gelsemium. Unlike all previous reviews of genus Gelsemium, to the best of our knowledge, the recently reported natural products from its endophytic fungi are first time summarized in this review. CONCLUSION: It is clearly suggested from the literature information that the structures and biological activities of Gelsemium have a wide range of attraction from folk to the community of scholars. However, as a highly toxic genus, the work on the detoxification mechanism and toxicology of Gelsemium is urgently needed before entering clinical research. It is noteworthy that the discussion about the relationship between structural and biological activities are a valuable topic of expectation, while the structural modification for active or toxic components may shed light on toxicological breakthrough. Besides the compounds from the plants of genus Gelsemium, the recently reported natural products from its endophytic fungi may provide a supplement for its ethnomedicinal uses and ethnological validity.

Structural Elucidation and Cytotoxic Activity of New Monoterpenoid Indoles from Gelsemium elegans.

Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1-2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM.

Biological Activities and Secondary Metabolites from Sophora tonkinensis and Its Endophytic Fungi.

The roots of Sophora tonkinensis Gagnep., a traditional Chinese medicine, is known as Shan Dou Gen in the Miao ethnopharmacy. A large number of previous studies have suggested the usage of S. tonkinensis in the folk treatment of lung, stomach, and throat diseases, and the roots of S. tonkinensis have been produced as Chinese patent medicines to treat related diseases. Existing phytochemical works reported more than 300 compounds from different parts and the endophytic fungi of S. tonkinensis. Some of the isolated extracts and monomer compounds from S. tonkinensis have been proved to exhibit diverse biological activities, including anti-tumor, anti-inflammatory, antibacterial, antiviral, and so on. The research progress on the phytochemistry and pharmacological activities of S. tonkinensis have been systematically summarized, which may be useful for its further research.