Neuroprotective potential of Celastrus paniculatus seeds against common neurological ailments: a narrative review

The most common human neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) etc. have been recognized to result from a complex interplay between genetic predisposition and defective cellular dynamics such as inappropriate accumulation of unfolded proteins, oxygen free radicals and mitochondrial dysfunction. The treatment strategies available today for these neurodegenerative ailments are only palliative and are incapable of restraining the progression of the disease. Hence, there is an immense requirement for identification of drug candidates with the ability to alleviate neuronal damage along with controlling progression of the disease. From time immemorial mankind has been relying on plants for treating varied types of dreadful diseases. Among the various medicinal plants used for treating various neurological ailments, Celastrus paniculatus (CP) popularly known as Jyotishmati or Malkangni is well known in the Ayurveda system of Indian Traditional Medicine whose seeds and seed oil have been used for centuries in treating epilepsy, dementia, facial paralysis, amnesia, anxiety, sciatica, cognitive dysfunctions etc. This review apart from specifying the phytochemical characteristics and traditional uses of C. paniculatus seeds and seed oil also exemplify the comprehensive data derived from various research reports on their therapeutic potential against some common neurological disorders.

Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K/AKT Signaling Pathway

Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg/kg body weight (b.w.)/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg/kg b.w./day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg/kg b.w./day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman–Keul’s test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K/AKT signaling pathways.

Neuroprotective Effect of Celastrus Paniculatus Seed Extract in Epilepsy and Epilepsy-Associated Cognitive Deficits

Purpose: Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus (C- paniculatus) seed extract on seizure severity and cognitive deficit following Pentylenetetrazole (PTZ) -induced chemical kindling model. Methods : PTZ kindling model was developed by daily administration of sub-convulsive dose of PTZ 30 mg/kg for 4 weeks. After 4 weeks of induction, the following treatment namely Sodium valproic acid (SVA) 200 mg/kg, C- paniculatus 500 mgkg, Pergolide 2 mg/kg alone and combination groups C- paniculatus 250 mgkg+ Pergolide 1 mg/kg and C- paniculatus 250 mgkg+ SVA 100 mg/kg were administered 30 minute prior to PTZ 30 mg/kg injection for a period of next 14 days. Neurobehavioral parameters Morris water maze test (MWM), Grip strength test (GPS) brain superoxide dismutase (SOD), Catalase, reduced glutathione (GSH) and dopamine level. Hematoxylin & Eosin (H&E) staining of hippocampus pyramidal layers Cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex were assessed. Results: C- paniculatus 500 mg/kg alone and combination groups C- paniculatus 250 mgkg+ Pergolide 1 mg/kg and Celastrus paniculatus 250 mgkg+ SVA 100 mg/kg significantly (p<0.05) reduced the seizure score, mean latency time, and distance traveled in MWM. However, no significant effect was seen in grip strength test. Biochemical analysis showed elevated antioxidant markers namely GSH, catalase, and SOD & elevated dopamine levels. C- paniculatus and its combination were also found significantly (p<0.05) protected against neuronal loss in hippocampus and frontal cortex as evidenced by H&E staining. Conclusion: C- paniculatus alone and its combination may have the potential to treat epilepsy and associated cognitive deficits.

ATTENUATION OF STRESS INDUCED URINARY BIOCHEMICAL CHANGES AND SCOPOLAMINE-INDUCED MEMORY LOSS BY HYDROALCOHOLIC SEED EXTRACT OF CELASTRUS PANICULATUS WILLD. IN RAT MODEL

Ayurveda uses seeds of Celastrus paniculatus to treat various stress related disorders. In the present investigation, the hydroalcoholic seed extract of C. paniculatus was evaluated for anti-stress activity by forced swim stress model. Vanillylmandelic acid and ascorbic acid were selected as non-invasive biomarkers to assess the anti-stress activity. Nootropic activity in rats was evaluated by conditioned avoidance response using Cook’s pole climbing apparatus, the antioxidant potential was determined based on the ability of the extract to scavenge hydroxyl radicals. Pretreatment with the extract significantly (p < 0.05) inhibited the stress induced urinary biochemical levels. The cognition was observed to be dose dependent. The extract also produced significant dose dependent inhibition of hydroxyl radicals. The present study provides scientific support for the anti-stress, antioxidant and nootropic activities of hydroalcoholic seed extract of C. paniculatus and substantiates the traditional claims for the usage of C. paniculatus willd. in stress induced disorders.

Phytochemistry and pharmacology of Celastrus paniculatus Wild.: a nootropic drug

Objectives Celastrus paniculatus Wild is an evergreen climbing shrub. The plant is of great significance in the traditional Indian System of Medicine, such as Ayurveda, Unani, and Siddha. The seeds and their oil are extensively used to treat neurological disorders such as cognitive dysfunction, paralysis, epilepsy, insomnia, and other ailments like rheumatism, arthritis, sciatica, and leprosy. This paper aims to highlight the nootropic activity of C. paniculatus and explore its phytochemistry, traditional uses, and other pharmacological activities. Methods All available information concerning C. paniculatus has been searched in the internationally accepted scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. Additional knowledge was gathered from the classical Textbooks and Unani Pharmacopoeia. Results C. paniculatus is a rich source of several secondary metabolites, such as β-Dihydroagarofuranoids sesquiterpenes, alkaloids (Celastrine, Celapanin, Celapagin, and paniculatin), flavonoids, terpenoid (β-amyrin, Lupeol, Pristimerin), sterols (β-sitosterol, campesterol, stigmasterol, α-tocopherol, γ-Tocopherol), fatty acid (palmitic, stearic, oleic, linoleic, linolenic acids) and non-fatty acids (Benzoic acid, Cinnamic acid). The various study shows that the extracts and active constituent of this plant possess potent nootropic activity. Besides nootropic activity, it has also been reported for anti-Alzheimer, anticonvulsant, antidepressant, antioxidant, analgesic, anti-inflammatory, antiarthritic, gastroprotective, anti-psoriatic, wound healing, antibacterial, antimalarial, and several other properties. Conclusions Several in vitro and in vivo trials confirm the conventional use of C. paniculatus in cognitive dysfunction. However, the relations between the possible mechanisms of other activities and traditional uses of the C. paniculatus remain indistinct. Still, pharmacological studies also explored the effects of C. paniculatus, which were not recognized in ancient times, such as cytotoxic, ACE inhibitor, and antidiabetic activities. These discoveries are may be beneficial in the development of the new drug to treat various diseases. It is also confirmed that the β-dihydroagarofuranoids exhibit significant AChE inhibitory, cytotoxic, antibacterial, and insecticidal effects. This versatile medicine is truly a life elixir. Considering the therapeutic importance of the C. paniculatus and the absence of any reported clinical studies, extensive clinical trials are needed to explore its memory enhancing and other activities.

Pharmacological Activities of Celastrus paniculatus Willd.: A Review

Current review includes medicinal importance and various pharmacological activities of Celastrus paniculatus Willd. Celastrus paniculatus Willd. belongs to Celastraceae family. It is a plant of medicinal importance and is being used in Ayurveda from a very long time to treat different disorders mainly brain related disoders. It is also known as ‘Tree of life’. It is commonly known as Malkangani and Jyothishmati in hindi and sanskrit respectively. Different studies have proved that it has various pharmacological activities which includes neuroprotective activity, rejuvenative activity, cardiovascular activity, analgesic activity, anti-inflammatory activity, antiinfertility activity, antioxidant activity, free radical scavenging activity anti-arthritic activity etc. It has been proved in various studies that Celastrus paniculatus willd. is a potent drug for improving memory and intellect. This manuscript reviews current information on various pharmacological and medicinal activities of Celastrus paniculatus.