Anti-arthritic and toxicological evaluation of ethanolic extract of Alternanthera bettzickiana in rats.

In many developing countries, medicinal plants have long been used for therapeutic purposes due to their low cost and toxicity. This study evaluated the safety and anti-arthritic potential of Alternanthera bettzickiana ethanolic extract (ABEE). Acute oral toxicity (OECD 425) was tested in the safety evaluation. A limit test was used to identify the LD50 value. For an acute oral toxicity study a dose of 2000 mg/kg of ABEE was given orally to the treatment group, and the control group received distilled water at a rate of 10 ml/kg. Biochemical, hematological, and histopathological analyses were performed after 14 days. A formaldehyde 2% w/v solution was injected via i.p. to rats of all groups to prepare the arthritic model. Five groups were divided into control (D.H2O), standard (Diclofenac), and three groups receiving the plant extract at dose levels of 125 mg/kg, 250 mg/kg, and 500 mg/kg respectively. Treatment was continued for 10 days. Paw diameter and hematological and biochemical variables were quantified. ELISA was performed for the estimation of inflammatory cytokines. In the acute oral toxicity study, no mortality or morbidity were observed, so the LD50 of this plant was greater than 2000 mg/kg. ABEE decreased the paw diameter with the restoration of hematological and biochemical changes. SOD and CAT levels were increased while decreasing the MDA, NO, TNF-α, and IL-6 levels in arthritic rats. It is concluded that the use of A. bettzickiana has low toxicity, and it can be used for the treatment of arthritis.

Prospective Evaluation of an Amide-Based Zinc Scaffold as an Anti-Alzheimer Agent: In Vitro, In Vivo, and Computational Studies.

Alzheimer's disease is the most common progressive neurodegenerative mental disorder associated with loss of memory, decline in cognitive function, and dysfunction of language. The prominent pathogenic causes of this disease involve deposition of amyloid-ß plaques, acetylcholine neurotransmitter deficiency, and accumulation of neurofibrillary tangles. There are multiple pathways that have been targeted to treat this disease. The inhibition of the intracellular cyclic AMP regulator phosphodiesterase IV causes the increase in CAMP levels that play an important role in the memory formation process. Organometallic chemistry works in a different way in treating pharmacological disorders. In the field of medicinal chemistry and pharmaceuticals, zinc-based amide carboxylates have been shown to be a preferred pharmacophore. The purpose of this research work was to investigate the potential of zinc amide carboxylates in inhibition of phosphodiesterase IV for the Alzheimer's disease management. Swiss Albino mice under controlled conditions were divided into seven groups with 10 mice each. Group I was injected with carboxymethylcellulose (CMC) at 1 mL/100 g dose, group II was injected with Streptozotocin (STZ) at 3 mg/kg dose, group III was injected with Piracetam acting as a standard drug at 200 mg/kg dosage, while groups IV-VII were injected with a zinc scaffold at the dose regimen of 10, 20, 40, and 80 mg/kg through intraperitoneal injection. All groups except group I were injected with Streptozotocin on the first day and third day of treatment at the dose of 3 mg/kg through an intracerebroventricular route to induce Alzheimer's disease. Afterward, respective treatment was continued for all groups for 23 days. In between the treatment regimen, groups were analyzed for memory and learning improvement through various behavioral tests such as open field, elevated plus maze, Morris water maze, and passive avoidance tests. At the end of the study, different biochemical markers in the brain were estimated like neurotransmitters (dopamine, serotonin and adrenaline), oxidative stress markers (superoxide dismutase, glutathione, and catalase), acetylcholinesterase (AchE), tau proteins, and amyloid-ß levels. A PCR study was also performed. Results showed that the LD50 of the zinc scaffold is greater than 2000 mg/kg. Research indicated that the zinc scaffold has the potential to improve the memory impairment and learning behavior in Alzheimer's disease animal models in a dose-dependent manner. At the dose of 80 mg/kg, a maximum response was observed for the zinc scaffold. Maximum reduction in the acetylcholinesterase enzyme was observed at 80 mg/kg dose, which was further strengthened and verified by the PCR study. Oxidative stress was restored by the zinc scaffold due to the significant activation of the endogenous antioxidant enzymes. This research ended up with the conclusion that the zinc-based amide carboxylate scaffold has the potential to improve behavioral disturbances and vary the biochemical markers in the brain.

Inhibition of Valproic Acid-Induced Prenatal Developmental Abnormalities with Antioxidants in Rats.

Valproic acid (VP) is a very effective therapy for the management of generalized epilepsy. However, its use during pregnancy leads to increased risk of teratogenesis and cognitive malfunctioning in postnatal growing children. Antioxidants are used commercially as a palliative therapy. This study compares the different antioxidants effects on VP-induced teratogenicity. Pregnant female rats (n = 80) were divided into eight groups (n = 10) as follows: Group I, control group; Group II, disease group valproic acid (500 mg/kg); Groups III and IV, treated with 2000 and 8000 mg/kg vitamin C, respectively; Groups V and VI, treated with selenium 100 and 200 µg/kg dose, respectively; and Groups VII and VIII, administered grape seed extract 300 and 600 mg/kg, respectively. Groups III-VIII received valproic acid (500 mg/kg) along with their respective treatments. All treatments were given via an oral route. The fetuses were double stained, and levels of superoxide dismutase (SOD), catalase (CAT), nitrite, glutathione (GSH), and malondialdehyde (MDA) were estimated. Resorption rate was significantly reduced in Vit. C treated groups at both dose levels. Maternal death rate was decreased remarkably in all treatment groups. Vit. C at a high dose (8000 mg/kg) and grape seed at a high dose (600 mg/kg) significantly reduced the incidence of delayed cervical ossification. The values of MDA were significantly reduced in all groups except the Vit. C group (2000 mg/kg). However, no significant elevation was observed in the values of SOD, CAT, and GSH. The current study concluded that vitamin C at a high dose (8000 mg/kg) and grape seed extract at a high dose (600 mg/kg) had partially protected the fetuses exposed to VP.