Solasodine

Description: IC50 Value: 12.17 ± 3.3 uM (Hela cell line)[1] Solasodine is a poisonous alkaloid chemical compound that occurs in plants of the Solanaceae family. Solasodine showed selective cytotoxicity against cervical cancer cell line (HeLa) and human myeloid leukemia cell line (U937). in vitro: Mouse embryonic teratocarcinoma P19 cells exposed to solasodine for 2 days followed by a 5-day washout differentiated into cholinergic neurons that expressed specific neuronal markers and displayed important axonal formation that continued growing even 30 days after treatment [2]. in vivo: A 2-week infusion ofsolasodine into the left ventricle of the rat brain followed by a 3-week washout resulted in a significant increase in bromodeoxyuridine uptake by cells of the ependymal layer, subventricular zone, and cortex that co-localized with doublecortin immunostaining, demonstrating the proliferative and differentiating properties of solasodine on neuronal progenitors. Solasodine treatment in rats resulted in a dramatic increase in expression of the cholesterol- and drug-binding translocator protein in ependymal cells, suggesting a possible role played by neurosteroid production in solasodine-induced neurogenesis. In GAD65-GFP mice that express the green fluorescent protein under the control of the glutamic acid decarboxylase 65-kDa promoter, solasodine treatment increased the number of GABAergic progenitors and neuroblasts generated in the subventricular zone and present in the olfactory migratory tract [2]. intraperitoneal (i.p.) injection of solasodine (25 mg/kg) significantly delayed (p < 0.01) latency of hind limb tonic extensor (HLTE) phase in the PCT-induced convulsions. In the MES model, solasodine significantly reduced (p < 0.001) duration of HLTE at 25, 50, and 100 mg/kg, i.p. in a dose-dependent manner [3]. Oral administration (80 mg/kg body wt/day for 30 days) of solasodine (extracted and isolated from the berries of the Solanum xanthocarpum) to intact dogs significantly decreased the epithelial cell height of cauda epididymides [4]. Toxicity: N/A Clinical trial: N/A

Anticonvulsant activity of solasodine isolated from Solanum sisymbriifolium fruits in rodents.[Pubmed:21062107]

Pharm Biol. 2011 Feb;49(2):194-9.

CONTEXT: Solanum sisymbriifolium Lam. (Solanaceae), commonly known as sticky nightshade, is traditionally used for central nervous system (CNS) disorders. Although Solasodine has been isolated from this plant, little is known about its anticonvulsant and CNS depressant actions. OBJECTIVE: We investigated anticonvulsant and CNS depressant effects of Solasodine isolated from S. sisymbriifolium using several experimental models. MATERIALS AND METHODS: Swiss albino mice (n=6) were employed for pentylenetetrazole (PTZ) and picrotoxin (PCT)-induced convulsions and thiopental-induced sleep time. Different groups of Wistar albino rats (n=6) were subjected to maximal electroshock (MES) test. Solasodine, a steroidal glycoalkaloid, was isolated from dried fruits of S. sisymbriifolium and identified by GC-MS. RESULTS: The results showed that intraperitoneal (i.p.) injection of Solasodine (25 mg/kg) significantly delayed (p < 0.01) latency of hind limb tonic extensor (HLTE) phase in the PCT-induced convulsions. In the MES model, Solasodine significantly reduced (p < 0.001) duration of HLTE at 25, 50, and 100 mg/kg, i.p. in a dose-dependent manner. Interestingly, Solasodine did not produce any significant reduction in PTZ-induced convulsions. Prior treatment of Solasodine (25, 50, and 100 mg/kg, i.p.) significantly potentiated thiopental-provoked sleep in a dose-dependent manner (p < 0.001). DISCUSSION AND CONCLUSION: Our study, for the first time, shows potent anticonvulsant and CNS depressant activities of Solasodine. It is likely that Solasodine, in part, is responsible for the anticonvulsant and sedative properties of S. sisymbriifolium. The future study should focus on the exact mechanism of action of Solasodine.

Development and validation a liquid chromatography mass spectrometry for determination of solasodine in rat plasma and its application to a pharmacokinetic study.[Pubmed:24922600]

J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jul 15;963:24-8.

Solasodine is a poisonous alkaloid chemical compound that occurs in plants of the Solanaceae family. A simple and selective liquid chromatography mass spectrometry method for determination of Solasodine in rat plasma was developed and validated over the range of 3-1,000 ng/mL. Chromatographic separation was achieved on a C18 (2.1 mmx50 mm, 3.5 mum) column with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. After addition of midazolam as internal standard (IS), liquid-liquid extraction by ethyl acetate was used as sample preparation. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification with target ions m/z 414 for Solasodine and m/z 326 for IS. Mean recoveries of Solasodine in rat plasma were in the range of 87.6-94.1%. Matrix effects for Solasodine were between 94.9% and 102.3%. Coefficient of variation of intra-day and inter-day precision were both <13%. The accuracy of the method ranged from 94.4% to 105.3%. The method was successfully applied to a pharmacokinetic study of Solasodine after oral administration of 20mg/kg in rats.

The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo.[Pubmed:21496476]

Neuroscience. 2011 Jun 2;183:251-64.

In this study, we explored the capacity of the naturally occurring compound Solasodine to promote neurogenesis in vitro and in vivo. Mouse embryonic teratocarcinoma P19 cells exposed to Solasodine for 2 days followed by a 5-day washout differentiated into cholinergic neurons that expressed specific neuronal markers and displayed important axonal formation that continued growing even 30 days after treatment. In vivo, a 2-week infusion of Solasodine into the left ventricle of the rat brain followed by a 3-week washout resulted in a significant increase in bromodeoxyuridine uptake by cells of the ependymal layer, subventricular zone, and cortex that co-localized with doublecortin immunostaining, demonstrating the proliferative and differentiating properties of Solasodine on neuronal progenitors. In addition, these data demonstrate that under our experimental conditions adult ependymal cells retrieved their proliferative and differentiating abilities. The GAP-43/HuD pathway was activated both in vitro and in vivo, suggesting a role in the differentiating process triggered by Solasodine. Solasodine treatment in rats resulted in a dramatic increase in expression of the cholesterol- and drug-binding translocator protein in ependymal cells, suggesting a possible role played by neurosteroid production in Solasodine-induced neurogenesis. In GAD65-GFP mice that express the green fluorescent protein under the control of the glutamic acid decarboxylase 65-kDa promoter, Solasodine treatment increased the number of GABAergic progenitors and neuroblasts generated in the subventricular zone and present in the olfactory migratory tract. Taken together, these results suggest that Solasodine offers an interesting approach to stimulate in situ neurogenesis from resident neuronal progenitors as part of neuron replacement therapy.

Solasodine protects rat brain against ischemia/reperfusion injury through its antioxidant activity.[Pubmed:24444441]

Eur J Pharmacol. 2014 Feb 15;725:40-6.

Ischemic stroke is the second leading cause of death worldwide. The major limitation of stroke management is the lack of clinically effective therapy. Antioxidants have been demonstrated as potent neuroprotective agents by enhancing the defense mechanism(s), whereas reducing the oxidative stress in the ischemic stroke models. In the present study, we evaluated neuroprotective potential of Solasodine, an antioxidant glycoalkaloid of Solanum species, against global model of ischemia in rats. Ischemia/reperfusion (I/R)-injury produced marked elevation in lipid peroxidation (LPO) and nitric oxide (NO), whereas superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were decreased in experimental animals. Prior administration of Solasodine (100 and 200mg/kg, p.o.) significantly heightened SOD, CAT, GSH and total thiols, whereas reduced LPO and NO levels in the brain. Interestingly, brain coronal sectioning and histopathology studies revealed a marked reversal of I/R-provoked neuronal damage in the Solasodine treatment groups. Taken together, our study, for the first time, demonstrates neuroprotective potential of Solasodine against global ischemia-induced cerebral injury in experimental rats. We propose that the neuroprotection offered by Solasodine could be attributed, at least in part, to its anti-oxidant property.

Effects of naturally occurring glucosides, solasodine glucosides, ginsenosides and parishin derivatives on multidrug resistance of lymphoma cells and leukocyte functions.[Pubmed:11317520]

In Vivo. 2001 Mar-Apr;15(2):151-6.

Solamargine, solasonine, ginsenosides and parishin-related compounds were investigated for their effects on mdr efflux pump of lymphoma cells, and their effects on T cell proliferative assays and cell mediated immune functions, antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell activity of human peripheral mononuclear cells. Solamargine and solasonine were the only drugs which inhibited all of the tested immune functions; however, ginsenoside Rc and Rd enhanced T cell proliferative assays and marginally increased the NK cell activity. The majority of the compounds were not able to reverse the multidrug resistance of mouse lymphoma cells. However, ginsenosides Rc, Rd and parishin C were able to moderately reduce the activity of the efflux pump. Parishin, parishin C and crude extract significantly enhanced the ADCC reaction.