Celastrus / Intellect tree

Celastrus paniculatus (of the family Celastraceae) is a large woody climbing shrub with a yellowish bark which is referred to as Jyothismati in Ayurveda, and the dark brown oil extracted from the seeds (seen as the medicinal component) called Jyothismati Oil,[1] Celastrus Oil,[2] or Malkanguni Oil.[3] It is a nootropic herb, and similar to most Medhya Rasayana (cognitive restorative agents from Indian medicine) it has some high praise warranting such names as 'The Elixir of Life'.[4]Traditional usage of this plant for medicinal purposes includes for the treatment of cognitive dysfunction, epilepsy, insomnia, rheumatism, gout, dyspepsia[1] as well as an abortifacient and depurative[5] while the oil has also been used as a massage oil for the medicinal treatment of arthritis and inflammatory skin conditions.[2] Although not traditionally used for these purposes, the seeds have been reported to be thermogenic, aphrodisiac, cardiotonic, and diuretic.[5]

The seeds are reported to be bitter in taste and hot in potency.[1]

Celastrus paniculatus appears to be a renowned plant of which the seeds (from within the fruits) are recommended for promotion of healthy cognition and nootropic purposes among other usages; the seeds are commonly made into an oil for usage either orally or as a massage oil

1.2. Composition

• • The sequesterpene alkaloids Celastrine and Celastrol (0.15% of arils)[5] as well as Celapanin, Celapanigin, and Celapagin[5]

  • Paniculatin and paniculatadiol (seed oil)[5][6]

  • Malkanguniol (a major consituent of the seed oil)[7]

  • Pristimerin[5]

  • Zeylasterone and Zeylasteral (bark extract)[5]

  • β-dihydroagarofuranoid sesquiterpenes[8]

  • Polyalcohol A-D[7] and the polyalcohol Dulcitol (flowers)[5]

  • Sequesterpene polyol esters such as Angulatueoid C, found in the chloroform extract and involved in intestinal relaxation[9][10]

  • β-sitosterol[5]

  • β-amyrin[5]

The composition of celastrus paniculatus appears to be relatively unknown at this point in time and the main bioactive is also not known. That being said, the classes of molecules most predominant in this plant appear to be the sequesterpene alkaloids and polyalcohols

2Neurology

2.1. Cholinergic Neurotransmission

A water extract from the seeds of Celastrus paniculatus, in a mouse (350-1,050mg/kg oral intake) and rat (500-1,500mg/kg) model of sodium nitrite induced amnesia, can inhibit acetylcholinesterase (increased during amnesia) by 13.17-19.33%, whereas the reference drug of 100mg/kg Piracetam inhibited it by 24.2%.[11] Elsewhere in a model of aluminum toxicity, Celastrus Oil is able to preserve the otherwise declining concentrations of acetylcholinesterase.[12]

In vitro, water extracts of the seeds failed to inhibit acetylcholinesterase at a concentration of 1µg/mL (a concentration where neuroprotection was observed)[13] and ethanolic and seed oils also fail;[4] chronic ingestion (14 days) of the seed oil at a dose able to prevent scopolamine induced amnesia did not alter cholinergic neurotransmission nor acetylcholinesterase activity.[14]

Although an indirect preservation of acetylcholinesterase concentrations has been noted secondary to neuroprotection, there does not appear to be any inherent alterations in acetylcholinesterase nor cholinergic activity with supplementation of celastrus paniculatus to rodents

2.2. Glutaminergic Neurotransmission

Water extracts (both hot and room temperature) as well as an acidic extraction of Celastrus paniculatus seeds have failed to exert neuroprotective effects at a concentration of 10ng/mL while concentrations of 100-1,000ng/mL (0.1-1µg/mL) of the extracts are able to protect cells from glutamate induced neurotoxicity.[13] Maximal efficacy was seen at 1µg/mL for the room temperature extraction and acidic (0.1µg/mL for the hot water extraction) and protection reached 21-28.6%[13]

The above neuroprotection was thought to be due to NMDA antagonist properties, as 2-4µg/mL of the water extracts cause dose-dependent and mostly reversible inhibition of NMDA induced currents reaching 48+/-3.8% inhibition.[13] This concentration also scavenges free radicals (superoxide and H2O2) suggesting a possible mechanism.[4]

The seeds of celastrus paniculatus appear to be protective against cell death from glutamate at a very low concentraiton, but the maximal protection observed is not too high. This may be, but is not confirmed, to be related to antioxidant properties

2.3. Adrenergic Neurotransmission

Oral ingestion of celastrus oil appears to be associated with less concentrations of noradrenaline in the rat brain alongside less urinary metabolites, suggesting less turnover.[15]

2.4. Dopaminergic Neurotransmission

Oral ingestion of celastrus oil appears to be associated with less concentrations of dopamine in the rat brain alongside less urinary metabolites, suggesting less turnover.[15]

2.5. Serotonergic Neurotransmission

Oral ingestion of celastrus oil appears to be associated with less concentrations of serotonin in the rat brain alongside less urinary metabolites, suggesting less turnover.[15]

2.6. Neurogenesis

Celastrus oil (intraperitoneal injections of approximately 1mL/kg or 3.2g/kg bodyweight for 45 days) has been found to increase cerebellum concentrations of protein and phospholipids as assessed by histological examination; this is thought to be indicative of increased myelination.[16]

Possible beneficial effects on myelin regeneration are hypothesized, but not well studied

2.7. Neuroprotection

Intraperitoneal injections of 0.5-1mL/kg (1.6-3.2g/kg) in rats who are subject to aluminum toxicity (a known neurotoxin[17] that somewhat mimicks Alzheimer's pathology[18]) for sixty days is able to attenuate learning deficits, with both doses being as protective as the reference drug Donepezil (0.5mg/kg).[12]

Standard doses used for cognitive enhancement appear to be somewhat neuroprotective against aluminum

10µg/mL of the hot water extract appeared to be cytotoxic to neuronal cells inherently, whereas this concentration of other extracts was not.[13]

High concentrations of celastrus paniculatus retain the potential to be neurotoxic themselves; this is appoximately 10-fold the concentration which is beneficial in vitro

2.8. Analgesia

An extract of celastrus paniculatus flowers (methanolic extract) appears to have analgesic properties in mice as assessed by tail immersion method, with 500mg/kg (peak efficacy) having a potency comparable to acetylsalicyclic acid at 300mg/kg.[19]

May have potent analgeisc properties, but the part of the plant used is not the commonly used supplement; it is unsure if the seeds also have analgesic properties

2.9. Stress and Anxiety

In mice given 200-400mg/kg of the oil from Celastrus paniculatus via intraperitoneal injections for seven days prior to stress testing was able to attenuate but not reverse changes in oxidative biomarkers (lipid peroxidation and antioxidative enzymes) seen with physical stress.[1]

1,000-1,500mg/kg of Celastrus oil for 14 days prior to anxiety testing in rats (open field and elevated maze plus) appears to exert anxiolytic effects either comparable or lesser than the reference drug of 1mg/kg Diazepam;[20] the addition of the two, or the combination of Celastrus oil and buspirone, failed to exert additive effects on anxiety reduction.[20]

Celastrus oil appears to have anxiolytic and anti-stress properties, and while they are respectable there is minimal evidence to support its usage for these goals

2.10. Memory and Learning

A water extract of the seeds of Celastrus paniculatus to mice (350-1,050mg/kg) and rats (500-1,500mg/kg) given after sodium nitrite induced amnesia appeared to cause dose-dependent improvements in memory retention with a potency slightly lesser than the reference drug Piracetam (100mg/kg).[11] Elsewhere, 14 days preload (but not a single dose) appeared to fully prevent scopolamine induced amnesia at 50-400mg/kg of the extract.[14]

When looking at anti-amnesiac properties, although there isn't much evidence it seems that acute usage of this herb is very weak at cognitive protection whereas prolonged usage may be more effective

At least one study, using celastrus paniculatus in albino rats exposed to a passive avoidance task, found cognitive enhancing effects (no reference drug)[15] while elsewhere a study on cognitive enhancement in otherwise healthy rats found that the water extract of the seeds (but not the ethanolic nor methanolic) at 100-300mg/kg for 14 days was able to significantly and time-dependently improve performance in shuttle-box and step-through performance tests; there was not a significant dose-dependent response, and the authors hypothesized that this was secondary to antioxidative effects.[21]

Elsewhere, one study in a model of aluminum toxicity noted that oral ingestion of 0.5-1mL/kg Celastrus Oil for 60 days exceeded the non-toxic control in passive avoidance (to a similar potency as 0.5mg/kg Donepezil).[12]

It appears that prolonged intake of the seed extract, likely due to a water soluble component, is able to increase cognitive performance in rodents. The exact mechanism and molecule underlying this effect is not currently known, and potency needs to be further assessed

3Cardiovascular Health

3.1. Lipoproteins and Cholesterol

A 50% methanolic extract of the seeds at 25-75mg/kg in male rats on a high fat diet noted a dose-dependent effect up to 65mg/kg which was able to effectively normalize all markers of lipid metabolism; a potency comparable to 5mg/kg atorvasatin (except for triglycerides and HDL-C, which atorvastatin nonsignificnatly outperformed).[22]

These beneficial changes were associated with increaes in fecal bile acids and sterols alongside a reduction in HMG-CoA activity.[22]

One study has noted anti artherogenic properties of the seed extract, practical relevance of this data is not known

4Interactions with Oxidation

4.1. In vitro

In vitro, methanolic extracts from Celastrus paniculatus appear to cause concentration dependent scavenging of superoxide anions with a potency lesser than that of methanolic extracts from Picrorhiza kurroa (of which 400µg/mL was equivalent to 25µM Trolox and 12-25µg/mL was as effective as 80mU/mL superoxide dismutase).[23] Relative to superoxide dismutase and Trolox (superoxide scavenging and DPPH assay, respectively) the highest concentrations of Celastrus paniculatus were only about 10-20% as potent and less than Ashwagandha (which was intermediate to celastrus and picrorhiza in this study).[23]

Has antioxidant potential, but this is significantly less than other tested herbal supplements

4.2. DNA Damage

A methanolic extract of celastrus paniculatus is able to preserve DNA from being damaged by H2O2at a concentration of 25µg/mL with a potency comparable to that of Ashwagandha and picrorhiza kurroa, all three of which were equivalent to 100µM Trolox (although picrorhiza trended to be most effective).[23] This concentration did not inhernetly damage DNA when not in the presence of an oxidative stress.[23]

The protective effects of celastrus paniculatus on DNA damage are comparable to other tested supplements in vitro; currently there is no evidence in living models

5Interactions with Organ Systems

5.1. Liver

Intraperitoneal injections of approximately 1mL/kg (3.2g/kg) of Celstrus Oil to rats appears to cause focal necrosis of the liver within 15 days of supplementation; continuing supplementation appears to cause a reduction in necrosis within 30 days and after 45 days there are no differences between supplementation and control.[24]

Has, oddly, been associated with causing necrosis of the liver and then repairing said necrosis; requires more research to delineate exactly what is happening

5.2. Intestines

Celastrus paniculatus appears to have a potent intestinal relaxation potential, with the IC50 values being 240+/-20ng/mL (rat ileum) and 260+/-20ng/mL (human ileum) and reaching 99% relaxation at highest efficacy (10μg/mL) and having efficacy as low as 100pg/mL.[25] This relaxation was reversible, and no desenstiization occurred after 10 consecutive administrations.[25] While the sequesterpenes have shown inhibitory potential in intestinal cells,[9] their inhibition reaching up to 31% at 1μg/mL is less potent than the whole extract.[9]

The relaxing effect appears to be inhibited by nifipedine, suggesting an inhibition of L-type Ca2+channels.[25]

Retains the potential to be a very potent intestinal relaxing agen

5.3. Testicles

Intraperitoneal injections of approximately 1mL/kg (3.2g/kg) for 45 days in rats appears to be assocaited with reductions in testicular weight with increases in phospholipids and cholesterol content of the testes; while histological examination did not show toxic effects, it did suggest a decrease in spermatogenesis and anti-fertility effects.[24]

Celastrus paniculata may have time-dependent anti-fertility actions

6Interactions with Cancer Metabolism

6.1. Breast

One sequesterpene from celastrus paniculatus ((1α,2α,8β,9β)-1,8-bis(acetyloxy)-2,9-bis(benzoyloxy)-14-hydroxy-β-dihydroagarofuran) is able to inhibit proliferation of breast cancer cells (MCF-7) with an IC50 of 17.1+/-1μM.[8]

7Safety and Toxicity

7.1. General

Acute ingestion of up to 5g/kg of Celastrus oil in albino rats has failed to exert toxic effects.[15]

7Scientific Support & Reference Citations

References

• 1. Lekha G, Mohan K, Samy IA Effect of Celastrus paniculatus seed oil (Jyothismati oil) on acute and chronic immobilization stress induced in swiss albino mice . Pharmacognosy Res. (2010)

1. Studies on biogenic amines and their metabolites in mentally retarded children in Celastrus oil therapy

2. A trial report on malkanguni oil with other indigenous drugs in the treatment of psychiatric cases

   1. Godkar PB, et al Celastrus paniculatus seed oil and organic extracts attenuate hydrogen peroxide- and glutamate-induced injury in embryonic rat forebrain neuronal cells . Phytomedicine. (2006)

3. Phyto-pharmacology of Celastrus paniculatus: An Overview

4. Paniculatadiol a new triterpene diol from Celastrus paniculatus Willd. Celastraceae

5. Stereochemistry of malkanguniol and stereostructures of some other related polyalcohols from Celastrus paniculatus Willd

• 1. Weng JR, Yen MH, Lin WY Cytotoxic constituents from Celastrus paniculatus induce apoptosis and autophagy in breast cancer cells . Phytochemistry. (2013)

  2. Borbone N, et al Identification of a new sesquiterpene polyol ester from Celastrus paniculatus . Planta Med. (2007)

  3. Borrelli F, et al New sesquiterpenes with intestinal relaxant effect from Celastrus paniculatus . Planta Med. (2004)

  4. Bhanumathy M, et al Nootropic activity of Celastrus paniculatus seed . Pharm Biol. (2010)

  5. Chakrabarty M, et al Cortico-hippocampal salvage in chronic aluminium induced neurodegeneration by Celastrus paniculatus seed oil: Neurobehavioural, biochemical, histological study . J Pharmacol Pharmacother. (2012)

  6. Godkar PB, et al Celastrus paniculatus seed water soluble extracts protect against glutamate toxicity in neuronal cultures from rat forebrain . J Ethnopharmacol. (2004)

  7. Gattu M, et al Reversal of scopolamine-induced deficits in navigational memory performance by the seed oil of Celastrus paniculatus . Pharmacol Biochem Behav. (1997)

  8. Nalini K, et al Effects of Celastrus paniculatus on passive avoidance performance and biogenic amine turnover in albino rats . J Ethnopharmacol. (1995)

  9. Bidwai PP, Wangoo D, Bhullar NK Effect of Celastrus paniculatus seed extract on the brain of albino rats . J Ethnopharmacol. (1987)

  10. Yokel RA The toxicology of aluminum in the brain: a review . Neurotoxicology. (2000)

  11. McLachlan DR, et al Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease . CMAJ. (1991)

  12. Ahmad F, Khan RA, Rasheed S Preliminary screening of methanolic extracts of Celastrus paniculatus and Tecomella undulata for analgesic and anti-inflammatory activities . J Ethnopharmacol. (1994)

  13. Rajkumar R, et al Evaluation of anxiolytic potential of Celastrus oil in rat models of behaviour . Fitoterapia. (2007)

  14. Kumar MH, Gupta YK Antioxidant property of Celastrus paniculatus willd.: a possible mechanism in enhancing cognition . Phytomedicine. (2002)

  15. Patil RH, Prakash K, Maheshwari VL Hypolipidemic Effect of Celastrus paniculatus in Experimentally Induced Hypercholesterolemic Wistar Rats . Indian J Clin Biochem. (2010)

  16. Russo A, et al Indian medicinal plants as antiradicals and DNA cleavage protectors . Phytomedicine. (2001)

  17. Bidwai PP, Wangoo D, Bhullar N Antispermatogenic action of Celastrus paniculatus seed extract in the rat with reversible changes in the liver . J Ethnopharmacol. (1990)

  18. Borrelli F, et al Potent relaxant effect of a Celastrus paniculatus extract in the rat and human ileum . J Ethnopharmacol. (2009)