Celastrus paniculatus oil ameliorates NF-KB mediated neuroinflammation and synaptic plasticity in the scopolamine-induced cognitive impairment rat model.

BACKGROUND AND AIM: Traditionally, Celastrus paniculatus Willd. (CP) oil has been utilized as a tranquilizer and memory enhancer. The present study investigated the neuropharmacological activity and efficacy of CP oil in ameliorating scopolamine-induced cognitive impairment in rats. EXPERIMENTAL PROCEDURE: Cognitive deficiency was induced in rats by administration of scopolamine (2 mg/kg intraperitoneal injection) for a period of 15 days. Donepezil served as a reference drug and CP oil was tested as both preventive and curative treatments. Animals' behaviour was assessed through the Morris water maze (MWM), novel object preference (NOR), and conditioned avoidance (CA) tests. Oxidative stress parameters, bioamine concentration (dopamine, noradrenaline, and 5-hydroxytryptamine), nerve growth factor (NGF), interleukin-6 (IL-6), nuclear factor kappa B (NF-кB), and tumor necrosis factor-alpha (TNFα) were estimated. Synaptophysin immunohistochemistry was performed. RESULTS: Our results showed that CP oil ameliorated behavioural deficits. It reduced latency to find a hidden platform in MWM. Reduced novel object exploration time and discrimination index (p < 0.05) in the NOR. Reduced step-down latency and normalized conditioned avoidance response (p < 0.001) in the CA test. CP oil increased dopamine, serotonin, norepinephrine, superoxide dismutase (SOD), glutathione, and catalase levels. It decreased malondialdehyde (MDA), acetylcholinesterase activity, IL-6, NF-кB (P < 0.001), TNFα, and NGF levels. Treatment showed approximate typical reactivity to synaptophysin. CONCLUSION: Our data is suggestive that CP oil treatment improves behavioural test outcomes, increases biogenic amine concentration, and decreases acetylcholinesterase activity, and neuroinflammatory biomarkers. It also restores synaptic plasticity. It thus improves cognitive functions against scopolamine-induced amnesia in rats by improving cholinergic function.

Protective effect of Celastrus paniculatus on cognitive function in glutamate-induced brain-injured mice by reducing the intracellular influx of Ca.

Present investigation evaluates the protective effect of Celastrus paniculatus (CP) on the cognitive function in neuronal injured mice. Neuronal injury was induced by oral administration of monosodium glutamate (MSG) at a dose of 1.66 g/kg/day for 30 days. Mice in the CP-treated group receives CP 30 mg/kg ip and CP + GGA-treated group received CP 30 mg/kg ip and glutamic acid (GGA, 1.5 mg/kg, ip) 30 min prior to the administration of MSG for 30 days. Assessment of cognitive function was done using Morris water maze. Level of inflammatory cytokines and production of reactive oxygen species (ROS) was estimated in the brain tissue of brain-injured mice. Moreover, intracellular concentration of Ca+ ion was estimated in the brain tissue and expression of Bcl-2, Bax, and caspase-3 protein was estimated in the brain tissue by western blot assay. Cognitive function was attenuated in CP-treated glutamate-injured mice. Data of the study suggest that treatment with CP reduces the level of inflammatory cytokines and production of ROS in the brain tissue compared to negative control group. There was reduction in the concentration of Ca+ ion in the neuronal cells in CP-treated group than negative control group of mice. Treatment with CP ameliorates the expression of Bax, Bcl-2, and caspase-3 in the brain tissue of glutamate-induced brain-injured mice. In conclusion, data of the study suggest that treatment with CP attenuates the cognitive function and neuronal apoptosis in glutamate-induced neuronal injury by reducing the concentration of intracellular Ca+ ion.

Probing the functions of friedelane-type triterpene cyclases from four celastrol-producing plants.

Triterpenes are among the most diverse plant natural products, and their diversity is closely related to various triterpene skeletons catalyzed by different 2,3-oxidosqualene cyclases (OSCs). Celastrol, a friedelane-type triterpene with significant bioactivities, is specifically distributed in higher plants, such as Celastraceae species. Friedelin is an important precursor for the biosynthesis of celastrol, and it is synthesized through the cyclization of 2,3-oxidosqualene, with the highest number of rearrangements being catalyzed by friedelane-type triterpene cyclases. However, the molecular mechanisms underlying the catalysis of friedelin production by friedelane-type triterpene cyclases have not yet been fully elucidated. In this study, transcriptome data of four celastrol-producing plants from Celastraceae were used to identify a total of 21 putative OSCs. Through functional characterization, the friedelane-type triterpene cyclases were separately verified in the four plants. Analysis of the selection pressure showed that purifying selection acted on these OSCs, and the friedelane-type triterpene cyclases may undergo weaker selective restriction during evolution. Molecular docking and site-directed mutagenesis revealed that changes in some amino acids that are unique to friedelane-type triterpene cyclases may lead to variations in catalytic specificity or efficiency, thereby affecting the synthesis of friedelin. Our research explored the functional diversity of triterpene synthases from a multispecies perspective. It also provides some references for further research on the relative mechanisms of friedelin biosynthesis.

Traditional uses, secondary metabolites, and pharmacology of Celastrus species - a review.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of genus Celastrus (Celastraceae) have been widely used in traditional Chinese medicine (TCM) and Indian medicine to treat cognitive dysfunction, epilepsy, insomnia, rheumatism, gout, and dyspepsia for thousands of years. AIM OF STUDY: We critically summarized the current evidence on the botanic characterization and distribution, ethnopharmacology, secondary metabolites, pharmacological activities, qualitative and quantitative analysis, and toxicology of Celastrus species to provide perspectives for developing more attractive pharmaceuticals of plant origin. MATERIALS AND METHODS: The relevant information on Celastrus species was gathered from worldwide accepted scientific databases via electronic search (Web of Science, SciFinder, PubMed, Elsevier, SpringerLink, Wiley Online, China Knowledge Resource Integrated, and Google Scholar). Information was also obtained from the literature and books as well as PhD and MSc dissertations. Plant names were validated by "The Plant List" (www.theplantlist.org). RESULTS: Comprehensive analysis of the above mentioned databases and other sources confirmed that ethnomedical uses of plants of Celastrus genus had been recorded in China, India, and other countries in Southern Asia. The phytochemical investigation revealed the presence of ß-dihydroagarofuranoids, diterpenoids, triterpenoids, tetraterpenes, phenylpropanoids, alkaloids, flavonoids, lignans, and others. The crude extracts and isolated constituents have exhibited a wide range of in vitro and in vivo pharmacological effects, including antitumor, cytotoxic, insecticidal, antimicrobial, anti-rheumatoid arthritis (RA), anti-inflammatory, anti-ageing and antioxidative, and neuroprotective activities. CONCLUSION: Plants of genus Celastrus have been confirmed to show a strong potential for therapeutic and health-maintaining effects, in light of their long traditional use and the phytochemical and pharmacological studies summarized here. Currently, pharmacological studies of this genus mainly focus on Celastrus paniculatus Willd. and Celastrus orbiculatus Thunb. Therefore, more pharmacological investigations should be implemented to support traditional uses of other medicinal plants of the genus Celastrus. Moreover, studies on the toxicity, bioavailability, and pharmacokinetics, in addition to clinical trials, are indispensable for assessing the safety and efficacy of the secondary metabolites or extracts obtained from plants belonging to this genus.

Molecular Analysis of Chinese Celastrus and Tripterygium and Implications in Medicinal and Pharmacological Studies.

Celastrus and Tripterygium species, which are used in traditional Chinese medicine, have attracted much attention due to their anti-tumor promoting and neuroprotective activities, in addition to their applications in autoimmune disorders. However, systematic relationships between them and among species are unclear, and it may disturb their further medicinal utilization. In the present study, the molecular analysis of combined chloroplast and nuclear markers of all Chinese Celastrus and Tripterygium was performed, and clear inter- and intra-genus relationships were presented. The result suggests that Tripterygium constitute a natural monophyletic clade within Celastrus with strong support value. Fruit and seed type are better than inflorescence in subgeneric classification. Chinese Celastrus are classified for three sections: Sect. Sempervirentes (Maxim.) CY Cheng & TC Kao, Sect. Lunatus XY Mu & ZX Zhang, sect. nov., and Sect. Ellipticus XY Mu & ZX Zhang, sect. nov. The phylogenetic data was consistent with their chemical components reported previously. Owing to the close relationship, several evergreen Celastrus species are recommended for chemical and pharmacological studies. Our results also provide reference for molecular identification of Chinese Celastrus and Tripterygium.

Celastrus and its bioactive celastrol protect against bone damage in autoimmune arthritis by modulating osteoimmune cross-talk.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by bone erosion and cartilage destruction in the joints. Many of the conventional antiarthritic drugs are effective in suppressing inflammation, but they do not offer protection against bone damage. Furthermore, the prolonged use of these drugs is associated with severe adverse reactions. Thus, new therapeutic agents that can control both inflammation and bone damage but with minimal side effects are sought. Celastrus is a Chinese herb that has been used for centuries in folk medicine for the treatment of various inflammatory diseases. However, its utility for protection against inflammation-induced bone damage in arthritis and the mechanisms involved therein have not been examined. We tested celastrus and its bioactive component celastrol for this attribute in the adjuvant-induced arthritis model of RA. The treatment of arthritic rats with celastrus/celastrol suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints as demonstrated by histology and bone histomorphometry. The protective effects against bone damage are mediated primarily via the inhibition of defined mediators of osteoclastic bone remodeling (e.g. receptor activator of nuclear factor-κB ligand (RANKL)), the deviation of RANKL/osteoprotegerin ratio in favor of antiosteoclastic activity, and the reduction in osteoclast numbers. Furthermore, both the upstream inducers (proinflammatory cytokines) and the downstream effectors (MMP-9) of the osteoclastogenic mediators were altered. Thus, celastrus and celastrol controlled inflammation-induced bone damage by modulating the osteoimmune cross-talk. These natural products deserve further consideration and evaluation as adjuncts to conventional therapy for RA.

Sesquiterpenes inhibiting NO production from Celastrus orbiculatus.

Two new (1 and 2) and one known (3) ß-dihydroagarofuran sesquiterpenes were isolated from the fruits of Celastrus orbicultus Thunb. Their structures were elucidated as 1ß,13-diacetoxy-8ß,9ß-dibenzoyloxy-ß-dihydroagarofuran (1), 1ß,13-diacetoxy-8α-hydroxy-9ß-benzoyloxy-ß-dihydroagarofuran (2), and 1ß,6α,13-triacetoxy-9α-benzoyloxy-ß-dihydroagarofuran (3), on the basis of spectroscopic data analyses. All the compounds exhibited inhibitory effects on LPS-induced nitric oxide production in murine microglial BV-2 cells.

[Effects of exogenous spermidine and spermine on Celastrus orbiculatus antioxidant system under soil NaHCO3 stress].

This paper studied the effects of foliar spraying spermidine and spermine on the leaf antioxidant system of Celastrus orbiculatus under soil NaHCO3 stress. The results showed that under the stress, spraying spermidine and spermine could significantly decrease the leaf O2-* production rate, H2O2 and MDA contents, and electrolyte leakage of C. orbiculatus (P < 0.05). Spraying spermidine increased the leaf SOD, CAT, POD and APX activities and GSH, CAR and Pro contents obviously, but had no effect on leaf AsA content. Spraying spermine also increased leaf POD and APX activities and GSH, CAR and Pro contents obviously, but had lesser effect on leaf SOD activity and AsA content, and even, caused a significant decrease in leaf CAT activity. In the meantime, spermidine and spermine effectively improved the growth of C. orbiculatus seedlings. It was suggested that under soil NaHCO3 stress, exogenous spermidine and spermine could improve the functions of membrane protective system and decrease the O2-* accumulation in C. orbiculatus leaves, and consequently, increase the C. orbiculatus tolerance to NaHCO3 exposure.