Picrotoxane Sesquiterpene Glycosides and a Coumarin Derivative from Coriaria nepalensis and Their Neurotrophic Activity

Abstract

Abstract:Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 1-3 and five semisynthetic congeners (1a-e) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells.

Traditional Uses of Medicinal Plants by Ethnic People in the Kavrepalanchok District, Central Nepal

“…The use of the ripe fruits and plant juice of Coriaria nepalensis ( Figure 3 D) in case of indigestion is unexpected, because the leaves and fruits of many Coriaria species are considered poisonous in Asia, due to the presence of coriamyrtin with convulsive effects [ 64 ]. Nevertheless, in Chinese Traditional Medicine this species is used to treat various diseases [ 65 ], and the leaf juice was indicated as antiseptic among the Newar community of Kathmandu District [ 32 ].…”

Phylogenetic relationship and characterization of the complete chloroplast genome of the Coriaria nepalensis Wall. in China, a least concern folk medicine

“…is a shrub belonging to single-genus of Coriaria (Coriariaceae family), and mainly distributed in the southern and southwestern of China. It is commonly used for the treatment of numbness, toothache, traumatic injury, and acute conjunctivitis in traditional Bai folk medicine (Jiang and Duan 2014), which are toxic to many animals (Wang et al 2016). Previous studies on C. nepalensis mainly focused on chemical components and biological characteristics (Wang et al 2016;Zhao et al 2018).…”

“…It is commonly used for the treatment of numbness, toothache, traumatic injury, and acute conjunctivitis in traditional Bai folk medicine (Jiang and Duan 2014), which are toxic to many animals (Wang et al 2016). Previous studies on C. nepalensis mainly focused on chemical components and biological characteristics (Wang et al 2016;Zhao et al 2018). However, the complete chloroplast (cp) genome sequence of C. nepalensis has not been reported so far.…”

Synthesis of C14-Desmethylene Corialactone D and Discovery of Inhibitors of Nerve Growth Factor Mediated Neurite Outgrowth

“…Recently, neurotrophic sesquiterpenoid natural products represented by the corialactones (Figure A) have become of interest to our laboratory because of their structural similarity to classic targets in natural product synthesis (Figure B), and an interest in exploring the value of recently developed synthetic methods in target-oriented synthesis and the biological properties associated with compositions of matter in this class. Corialactones have been found in terrestrial Himalayan shrubs ( Coriaria nepalensis ) that have been used as a Chinese herbal medicine for the treatment of numbness, toothache, traumatic injury, and acute conjunctivitis, among other ailments . Notably, two sesquiterpenes identified from this terrestrial source have been claimed to be clinically useful for the treatment of schizophrenia. , Despite the structural similarity of corialactone sesquiterpene natural products to the potent GABA antagonist picrotoxinin (described as one of the most toxic agents of plant origin) and the modestly analgesic alkaloid dendrobine (Figure B), , sesquiterpenes from the roots of Coriaria nepalensis appear to have a unique and nontoxic pharmacological profile in vitro at concentrations up to 10 μM [PC-12 (neuro), HCT-8 (colon), HepG2 (liver), BGC-823 (gastric), A549 (lung epithelia), and SKOV3 (ovarian) - MTT assays] .…”

“…Corialactones have been found in terrestrial Himalayan shrubs ( Coriaria nepalensis ) that have been used as a Chinese herbal medicine for the treatment of numbness, toothache, traumatic injury, and acute conjunctivitis, among other ailments . Notably, two sesquiterpenes identified from this terrestrial source have been claimed to be clinically useful for the treatment of schizophrenia. , Despite the structural similarity of corialactone sesquiterpene natural products to the potent GABA antagonist picrotoxinin (described as one of the most toxic agents of plant origin) and the modestly analgesic alkaloid dendrobine (Figure B), , sesquiterpenes from the roots of Coriaria nepalensis appear to have a unique and nontoxic pharmacological profile in vitro at concentrations up to 10 μM [PC-12 (neuro), HCT-8 (colon), HepG2 (liver), BGC-823 (gastric), A549 (lung epithelia), and SKOV3 (ovarian) - MTT assays] . Piquing our interest in corialactones as synthetic targets, glycosides of sesquiterpenes in this class, as well as semisynthetic variants ( 1 – 3 ; Figure A), have been reported as neurotrophic agents, despite a variable nature of C14 (i.e., active agents are reported that contain an allylic alcohol, allylic halide, or an electrophilic enone in this region of the natural product structure) .…”