Herbal remedies in the management of hyperuricemia and gout: A review of in vitro, in vivo and clinical evidences.

Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.

Assessment of the Phytochemical Profile, Antioxidant Capacity, and Hepatoprotective Effect of Andrographis paniculata against CCl4-Induced Liver Dysfunction in Wistar Albino Rats.

Recent studies have highlighted the necessity to thoroughly evaluate medicinal plants due to their therapeutic potential. The current study delves into the phytochemical profile, antioxidant capacity, and hepatoprotective effect of Andrographis paniculata. The investigation specifically targets its effectiveness in mitigating liver dysfunction induced by carbon tetrachloride (CCl4) in Wistar albino rats, aiming to uncover its promising role as a natural remedy for liver-related ailments. A. paniculata leaf extract was screened for phytoconstituents and antioxidant and hepatoprotective effects in Wistar albino rats against CCl4-induced liver dysfunction. Phytochemical analysis revealed the presence of flavonoids, alkaloids, and phenolic compounds in all extracts. The phenolic concentration ranged from 10.23 to 19.52 mg gallic acid per gram of the sample, while the highest flavonoid concentration was found in the ethanol fraction (8.27 mg rutin equivalents per gram). The antioxidant activity varied from 10.23 to 62.23. GC-MS analysis identified several phytochemicals including octadecanoic acid, stigmasterol, phenanthrenecarboxylic acid, and others. Effects of the ethanol extract of A. paniculata were evaluated in four groups of animals. Biochemical estimations of serum glutamine oxaloacetate transaminase, serum glutamine pyruvate transaminase, and serum bilirubin were significantly higher (p < 0.05) in the CCl4-treated group. Treatment with 300 mg/kg b.w. of the ethanol extract of A. paniculata significantly (p < 0.05) decreased these serum enzymes. Lipid peroxidation levels in carbon tetrachloride-treated animals showed a substantial (p < 0.05) rise when compared to untreated animals, while the lipid peroxidation levels were considerably (p < 0.05) reduced after treatment with ethanol extract at 300 mg/kg b.w. Liver biochemical catalase activities were significantly reduced in the carbon tetrachloride-treated animals. The results of this study conclusively demonstrate that A. paniculata extracts are a rich source of phytochemicals and possess significant antioxidant, free radical scavenging, and hepatoprotective properties.

Pharmacological melioration by Selenium on the toxicity of tellurium in neuroendocrine centre (Pituitary Gland) in male wistar rats: A mechanistic approach.

PURPOSE: The present research was designed to evaluate the toxicity of tellurium and its prevention by selenium on the pituitary gland in male Wistar rats. METHODS: 30 rats were used weighing 200-250 gm, and randomly divided them into five groups. Each group contained an equal number of animals. Group-1 was nominated as control group. Group-2 received an intraperitoneal dose of selenium 0.3  mg per kg body wt. Group-3 was administered with tellurium 4.15 mg per kg body wt. Group-4 was given low-dose (L) of both selenium 0.15 and tellurium 2.075, Group-5 was given High-dose (H) of both selenium 0.3 and tellurium 4.15 mg/kg body wt. orally once in a day. After 15 days of dosing, the behavioral activities- motor co-ordination rotarod and grip strength test were measured. On 16th-day animals were sacrificed and activity of LPO, GSH, caspase-3, caspase-9, GPx, GR, SOD, catalase, and AChE were performed on the pituitary gland as per standard method reported. RESULTS: Se when given together with Te, significantly protects the motor coordination up to 32.5%, and also protects the grip strength up to 75% in group 4 and 5 respectively as compared to group- 3. Se + Te treatment protects the activity of TBARS up to 48.68% and GSH is 58%. As compared to control, it protects caspase-3 up to 118% and caspase-9 up to 83%. The level of AChE was also observed to be modulated by the administration of Se in Group- 4 and 5. Se + Te protected AChE up to 28.6%. Similar findings were observed for the biochemical activities of GPx (140% protection), SOD (458%), GR (159%), and catalase (95%) activities that were protected significantly Se + Te in Group- 4 and 5. CONCLUSION: Selenium dose-dependently protects behavioral activities. It also protects apoptosis, oxidative stress, and AChE activities in the pituitary gland.

Bacopa monniera ameliorates cognitive impairment and neurodegeneration induced by intracerebroventricular-streptozotocin in rat: behavioral, biochemical, immunohistochemical and histopathological evidences.

The standardized extract of Bacopa monniera (BM) is a complex mixture of ingredients with a uniquely wide spectrum of neuropharmacological influences upon the central nervous system including enhanced learning and memory with known antioxidant potential and protection of the brain from oxidative damage. The present study demonstrates the therapeutic efficacy of BM on cognitive impairment and oxidative damage, induced by intracerebroventricular injection of streptozotocin (ICV-STZ) in rat models. Male Wistar rats were pre-treated with BM at a selected dose (30 mg/Kg) given orally for 2 weeks and then were injected bilaterally with ICV-STZ (3 mg/Kg), while sham operated rats were received the same volume of vehicle. Behavioral parameters were subsequently monitored 2 weeks after the surgery using the Morris water maze (MWM) navigation task then were sacrificed for biochemical, immunohistochemical (Cu/Zn-SOD) and histopathological assays. ICV-STZ-infused rats showed significant loss in learning and memory ability, which were significantly improved by BM supplementation. A significant increase in thiobarbituric acid reactive species and a significant decrease in reduced glutathione, antioxidant enzymes in the hippocampus were observed in ICV-STZ rats. Moreover, decrease in Cu/Zn-SOD expression positive cells were observed in the hippocampus of ICV-STZ rats. BM supplementation significantly ameliorated all alterations induced by ICV-STZ in rats. The data suggest that ICV-STZ might cause its neurotoxic effects via the production of free radicals. Our study demonstrates that BM is a powerful antioxidant which prevents cognitive impairment, oxidative damage, and morphological changes in the ICV-STZ-infused rats. Thus, BM may have therapeutic value for the treatment of cognitive impairment.

Cathinone, an active principle of Catha edulis, accelerates oxidative stress in the limbic area of swiss albino mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cathinone hydrochloride is an active principle of the khat plant (Catha edulis) that produces pleasurable and stimulating effects in khat chewers. To the best of our knowledge no data of cathinone on oxidative stress in limbic areas of mice is available. This is the first study of cathinone on oxidative stress in limbic areas of the brain in Swiss albino male mice. MATERIALS AND METHODS: The animals were divided into four groups. Group-I was the control group and received vehicle, while groups-II to IV received (-)-cathinone hydrochloride (0.125, 0.25 and 0.5 mg/kg body wt., i.p.) once daily for 15 days. RESULTS: The level of lipid peroxidation (LPO) was elevated dose-dependently and was significant (p<0.05, p<0.01) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. In contrast, the content of reduced glutathione (GSH) was decreased significantly (p<0.01, p<0.001) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. The activity of antioxidant enzymes (GPx, GR, GST, CAT, and SOD) was also decreased dose-dependently: the decreased activity of GPx, GR, catalase and SOD was significant with doses of 0.25 and 0.5 mg of cathinone as compared to control group, while the activity of GST was decreased dose-dependently and was significant with 0.5mg of cathinone as compared to control group. CONCLUSIONS: The results indicate that the cathinone generated oxidative stress hampered antioxidant enzymes, glutathione and lipid peroxidation.

S-allyl cysteine mitigates oxidative damage and improves neurologic deficit in a rat model of focal cerebral ischemia.

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The present study examined the hypothesis that S-allyl cysteine (SAC), organosulfur compounds found in garlic extract, would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). To test this hypothesis, male Wistar rats were subjected to MCAO for 2 hours and 22-hour reperfusion. S-allyl cysteine was administered (100 mg/kg, b.wt.) intraperitoneally 30 minutes before the onset of ischemia and after the ischemia at the interval of 0, 6, and 12 hours. After 24 hours of reperfusion, rats were tested for neurobehavioral activities and were killed for the infarct volume, estimation of lipid peroxidation, glutathione content, and activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase). S-allyl cysteine treatment significantly reduced ischemic lesion volume, improved neurologic deficits, combated oxidative loads, and suppressed neuronal loss. Behavioral and biochemical alterations observed after MCAO were further associated with an increase in glial fibrillary acidic protein and inducible nitric oxide expression and were markedly inhibited by the treatment with SAC. The results suggest that SAC exhibits exuberant neuroprotective potential in rat ischemia/reperfusion model. Thus, this finding of SAC-induced adaptation to ischemic stress and inflammation could suggest a novel avenue for clinical intervention during ischemia and reperfusion.

Silymarin protects neurons from oxidative stress associated damages in focal cerebral ischemia: a behavioral, biochemical and immunohistological study in Wistar rats.

Cerebral stroke is the third largest cause of death and the severe leading cause of disability, thus have astronomical financial and social burden worldwide. Accumulated evidence suggests that ROS can be scavenged through utilizing natural antioxidant compounds present in foods and medicinal plants. In this study, we examined whether silymarin, an antioxidant, present in the milk of thistle can prevent or slowdown neuronal injury in focal cerebral ischemia. Male Wistar rats were pre-treated with silymarin (200mg/kg body weight, dissolved in 0.3 % sodium carboxymethyl cellulose, once orally) for 15 days. On day 16, they underwent a transient 2h suture-occlusion of the middle cerebral artery followed by 22 h of reperfusion. Rats were tested for neurobehavioral activity after 22 h reperfusion. Silymarin was found to be successful in upregulating the antioxidant status and lowering the apoptotic responses, and functional recovery returned close to the baseline. This study revealed that silymarin, a naturally occurring flavone from the milk thistle (Silybum marianum), may be helpful in slowing down the progression of neurodegeneration in focal cerebral ischemia. These results suggest that the neuroprotective potential of silymarin is mediated through its anti-oxidative and anti-apoptotic properties.

Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: behavioral, neurochemical and immunohistochemical studies.

Curcumin, the active principle of turmeric used in Indian curry is known for its antitumor, antioxidant, antiarthritic, anti-ischemic and anti-inflammatory properties and might inhibit the accumulation of destructive beta-amyloid in the brains of Alzheimer's disease patients. A Parkinsonian model in rats was developed by giving 6-hydroxydopamine (10 µg/2 µl in 0.1% ascorbic acid-saline) in the right striatum. After 3 weeks of lesioning, the behavior activities (rotarod, narrow beam test, grip test and contra-lateral rotations) were increased in a lesioned group as compared to a sham group and these activities were protected significantly with the pretreatment of curcumin. A significant protection on lipid peroxidation, glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, tyrosine hydroxylase and D(2) receptor binding was observed in the striatum of lesioned group animals pretreated with 80 mg/kg body weight of curcumin for 21 days as compared to lesion group animals. No significant alterations on behavior and biochemical parameters were observed in sham group animals and the animals of sham group pretreated with curcumin. This study indicates that curcumin, which is an important ingredient of diet in India and also used in various systems of indigenous medicine, is helpful in preventing Parkinsonism and has therapeutic potential in combating this devastating neurologic disorder.

Synergistic effect of selenium and melatonin on neuroprotection in cerebral ischemia in rats.

The synergistic scavenger effects of selenium and melatonin collectively we called Se-Mel was studied on the prevention of neuronal injury induced by ischemia/reperfusion. Male Wistar rats were treated with sodium selenite (0.1 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) 30 min before the middle carotid artery occlusion (MCAO) and immediately after MCAO to male Wistar rats and was continued for 3 days once daily at the interval of 24 h. Behavioral activity (spontaneous motor activity and motor deficit) was improved in Se-Mel-treated rats as compared to MCAO group rats. The level of glutathione and the activity of antioxidant enzymes was depleted significantly while the content of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide radical (NO(·)) was increased significantly in MCAO group. Systemic administration of Se-Mel ameliorated oxidative stress and improves ischemia/reperfusion-induced focal cerebral ischemia. Se-Mel also inhibited inducible nitric oxide synthase expression in Se-Mel+MCAO group as compared to MCAO group rats. Thus, Se-Mel has shown an excellent neuroprotective effect against ischemia/reperfusion injury through an anti-ischemic pathway. In conclusion, we demonstrated that the pretreatment with Se-Mel at the onset of reperfusion, reduced post-ischemic damage, and improved neurological outcome following transient focal cerebral ischemia in male Wistar rat.

Amelioration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced behavioural dysfunction and oxidative stress by Pycnogenol in mouse model of Parkinson's disease.

Increased oxidative stress is implicated in the pathogenesis of Parkinson's disease in which dopaminergic neurons are intrinsically susceptible to oxidative damage. Swiss albino mice were pretreated with Pycnogenol (PYC), an extract of Pinus maritime bark [20 mg/kg body weight, intraperitoneally (i.p.)] once daily for 15 days. Thereafter, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (20 mg/kg body weight, intraperitoneally) was given four times at 2-hour intervals on 1 day only. Behaviours were altered in the MPTP group as compared with the vehicle-treated group and were restored in the PYC-pretreated MPTP group. The activity of antioxidant enzymes and the content of glutathione were significantly depleted in the MPTP-induced Parkinsonian group. The MPTP group pretreated with PYC showed significant protection of the activity of antioxidant enzymes and glutathione content when compared with the vehicle-treated MPTP group. A significantly elevated level of thiobarbituric acid reactive substances in the MPTP group was decreased significantly in the animals pretreated with PYC. An increase in the number of dopaminergic D2 receptors and decrease in the level of dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid in the striatum were observed after MPTP injection, and restored significantly after PYC pretreatment. Thus, PYC may be used to prevent or reduce the deterioration caused by free radicals, thereby preventing subsequent behavioural and biochemical changes that occur in Parkinsonian mice.

Rutin protects the neural damage induced by transient focal ischemia in rats.

Free radical induced neural damage is implicated in cerebral ischemia-reperfusion (IR) injury and antioxidants are reported to have neuroprotective activity. The present study was designed to assess the neuroprotective role of rutin (Vitamin P), and mechanism of action. The middle cerebral artery (MCA) of an adult male Wistar rat was occluded for 2 h and reperfused for 22 h. The administration of rutin (25 mg/kg bwt., orally) once daily for 21 days before middle cerebral artery occlusion (MCAO) showed marked reduction in infarct size, reduced the neurological deficits in terms of behaviors, suppressed neuronal loss and diminished the p53 expression in MCAO rats. A significantly depleted activity of antioxidant enzymes, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) and content of glutathione (GSH) in MCAO group were protected significantly in MCAO group pretreated with rutin. Conversely, the elevated level of thiobarbituric acid reactive species (TBARS), H(2)O(2) and protein carbonyl (PC) in MCAO group was attenuated significantly in rutin-pretreated group when compared with MCAO group. These results indicate that rutin attenuates ischemic neural apoptosis by reducing the expression of p53, preventing morphological changes and increasing endogenous antioxidant enzymatic activities. Thus, rutin treatment may represent a novel approach in lowering the risk or improving the function of ischemia-reperfusion brain injury-related disorders.

Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer's type.

Selenium (Se), a nutritionally essential trace element with known antioxidant potential, protects the brain from oxidative damage in various models of neurodegeneration. Intracerebroventricular-streptozotocin (ICV-STZ) in rats causes impairment of brain glucose and energy metabolism along with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (SDAT). The present study demonstrates the therapeutic efficacy of Se on cognitive deficits and oxidative damage in ICV-STZ in rats. Male Wistar rats were pre-treated with sodium selenite, a salt of Se (0.1 mg/kg; body weight) for 7 days and then were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle. After two ICV-STZ infusions, rats were tested for memory deficits in passive avoidance and Morris water maze (MWM) tests and then were sacrificed for biochemical and histopathological assays. ICV-STZ-infused rats showed significant loss in learning and memory ability, which were significantly improved by Se supplementation. A significant increase in thio-barbituric acid reactive species (TBARS), protein carbonyl (PC) and a significant decrease in reduced glutathione (GSH), antioxidant enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and adenosine triphosphate (ATP) in the hippocampus and cerebral cortex and choline acetyltransferase (ChAT) in hippocampus were observed in ICV-STZ rats. Se supplementation significantly ameliorated all alterations induced by ICV-STZ in rats. Our study reveals that Se, as a powerful antioxidant, prevents cognitive deficits, oxidative damage and morphological changes in the ICV-STZ rats. Thus, it may have a therapeutic value for the treatment of SDAT.