Antidiabetic potential of flavonoids from Artemisia macrocephalla Jaquem in streptozotocin-induced diabetic rats: Pharmacological and biochemical approach.

Plants belongs to Asteraceae family are reported to be rich in major phytochemical including flavonoids and are documented to acquire antidiabetic response. Antidiabetic effects of salvigenin, eupatilin and cirsilineol were screened on in-vitro enzyme inhibition and in-vivo streptozotocin animal models. Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) produced antidiabteic responses in streptozotocin model for diabetes. All natural flavonoids reduces the blood glucose level to a significant level (*P<0.05, **P<0.01, ***P<0.001, n=8) but promising results were observed in eupatilin at dose of 7.5mk/kg (364.12±4.3 to 128.41±4.2mg/dL, n=8) and at dose of 7.5mk/kg 363.65±4.8 to 126.14±5.1mg/dL, n=8). Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) for 28 days showed a substantial fall (*P<0.05, **P<0.01, ***P<0.001, n=8) in total cholesterol, LDL and triglcerides (TGs) in comparison to diabetic model. The isolated flavonoids reduced considerably the serum ALP, SGPT and SGOT in rats intoxicated with streptozotocin. The results indicate that the flavonoids may be useful in the development of new antidiabetic drugs.

A possible anti-inflammatory mechanism of ethyl acetate extracts of Teucrium stocksianum Bioss.

BACKGROUND: Teucrium stocksianum (T. stocksianum) is one of the important members of the genus Teucrium which contains numerous biologically active compounds. Traditionally, it is used for the treatment of fever, pain, as expectorant and blood purifier. Researchers are trying to discover plants origin, novel and safe remedies for the management of various ailments. The present study was aimed to determine the possible anti-inflammatory mechanism of ethyl acetate extract of T. stocksianum. METHODS: Preliminary, the ethanolic extract and sub-fractions were screened for anti-inflammatory potential at doses of 100, 200 and 300 mg/kg (i.p) body weight, using carrageenan induced paw edema test in mice. In-order to determine the possible mechanism of anti-inflammatory effect, the ethyl acetate fraction was ascertained with different phlogistic agents like histamine, bradykinin, prostaglandins E2 and arachedonic acid via paw edema test in mice. RESULTS: The ethanolic extract and sub-fractions of T. stocksianum displayed marked to moderate anti-inflammatory activity in a carrageenan induced paw edema test in mice. Among the sub-fractions, ethyl acetate fraction (EAF) demonstrated excellent (66%) anti-inflammatory action at the highest tested dose (300 mg/kg) that reached to the maximum value at 3rd hour after carrageenan injection and remained significant (***P<0.001) till 5th hour of test sample administration. EAF revealed moderate effect against the paw edema induced by histamine (31.048%) while non-significant results (18.148%) were observed against the edema induced by bradykinin. The extract demonstrated significant (66.23-73.076%) anti-inflammatory potential against the edematogenic effect of prostaglandin E2. Moreover, the extract also significantly inhibited (51.33%) the paw edema induced by arachedonic acid. CONCLUSION: Our results suggest that the EAF has dual action and produced the anti-inflammatory effect by blocking both pathways of arachedonic acid metabolites (cyclooxygenase and lipoxygenase). Thus validating the traditional use of T. stocksianum and could provide a source of novel, effective and safe drug for the treatment of inflammation.

Investigation of anti-nociceptive, anti-inflammatory potential and ADMET studies of pure compounds isolated from Isodon rugosus Wall. ex Benth.

The strong ethnopharmacological utilization of Isodon rugosus Wall. Ex. Benth is evident in the treatment of several types of pain and inflammation, including toothache, earache, abdominal pain, gastric pain, and generalized body pain and inflammation. Based on this background, the antinociceptive effects of the crude extract, various fractions, and essential oil have been reported previously. In this research work, we isolate and characterize pure bioactive compounds from I. rugosus and evaluate possible mechanisms using various in vivo and in vitro models. The pure compounds were analyzed for analgesic and anti-inflammatory activities through various assays. The column chromatography of the chloroform fraction of I. rugosus led to the identification of two pure compounds, i.e., 1 and 2. Compound 1 demonstrated notable inhibition (62% writhing inhibition, 72.77% COX-2 inhibition, and 76.97% 5-LOX inhibition) and anti-inflammatory potential (>50% paw edema inhibition at various intervals). The possible mechanism involved in antinociception was considered primarily, a concept that has already been elucidated through the application of naloxone (an antagonist of opioid receptors). The involvement of adrenergic receptors was investigated using a hot plate model (an adrenergic receptor antagonist). The strong ethnomedicinal analgesic background of I. rugosus, supported by previous reports and current observations, leads to the conclusion that I. rugosus is a potential source of antinociceptive and anti-inflammatory bioactive compounds. It may be concluded from the results that the isolated analgesic compounds of I. rugosus may be a possible alternative remedy for pain and inflammation management with admirable efficacy and safety profiles.

Synthesis, Antioxidant, and Antidiabetic Activities of Ketone Derivatives of Succinimide.

The prevalence of diabetes mellitus is persistently increasing globally creating a serious public health affliction. Diabetes mellitus is categorized into two major types designated as type I and Type II. Type I diabetes mellitus is characterized by complete lack of secretion of insulin, while Type II diabetes mellitus is the resistance of peripheral tissues to the action of insulin and inadequate compensatory secretion of insulin. Chronic hyperglycemia associated with diabetes causes failure of cardiovascular system, nervous system, kidneys, and eyes. At present, different types of drugs are used for the management of diabetes, but each of them is associated with more or less serious side effects. Therefore, we need to develop new therapeutic agents that have better efficacy and safety profile. In this study, three ketone derivatives of succinimides were synthesized based on Michael addition and characterized using NMR. All the synthesized compounds were checked for their in vitro α-amylase and α-glucosidase inhibitory activities. Further the synthesized compounds were also explored for their antioxidant activities, i.e, DPPH and ABTS assays. Based on the in vitro results, the synthesized compounds were further evaluated for in vivo antidiabetic activity. The synthesized compounds were (2-oxocyclohexyl)-1-phenylpyrrolidine-2,5-dione (BW1), benzyl-3-(2-oxocyclohexyl) pyrrolidine-2,5-dione (BW2), and (4-bromophenyl)-3-(2-oxocyclohexyl) pyrrolidine-2,5-dione (BW3). BW1 showed the highest inhibitory activity for DPPH causing 83.03 ± 0.48 at 500 µg/ml with IC50 value of 10.84 µg/ml and highest inhibitory activity for ABTS causing 78.35 ± 0.23 at 500 µg/ml with IC50 value of 9.40 µg/ml against ascorbic acid used as standard. BW1 also exhibited the highest activity against α-amylase and α-glucosidase inhibition causing 81.60 ± 0.00 at concentrations of 500 µg/ml with IC50 value of 13.90 µg/ml and 89.08 ± 1.04 at concentrations of 500 µg/ml with IC50 value of 10.49 µg/ml, respectively, against the standard drug acarbose.

Comparative in-vitro anti-inflammatory, anticholinesterase and antidiabetic evaluation: computational and kinetic assessment of succinimides cyano-acetate derivatives.

This research was planned to synthesize cyano-acetate derivatives of succinimide and evaluate its comparative biological efficacy as anti-inflammatory, anti-cholinesterase and anti-diabetic, which was further validated by molecular docking studies. The three cyano-acetate derivatives of succinimide including compound 23 Methyl 2-cyano-2-(2,5-dioxopyrrolidin-3-yl)acetate, compound 31 Methyl 2-cyano-2-(1-methyl-2,5-dioxopyrrolidin-3-yl)acetate and compound 44 Methyl 2-cyano-2-(1-ethyl-2,5-dioxopyrrolidin-3-yl) acetate were synthesized. The mentioned compounds were checked for in vitro anti-inflammatory, anti-cholinesterase and anti-diabetic (α-amylase inhibition) activity. To validate the in vitro results, computational studies were carried out using molecular operating environment to analyse the BE, i.e. binding energies of all synthesized compounds against the respective enzymes. The Compounds 23, 31, 44 exhibited anti-inflammatory via inhibiting COX-2 (IC50 value of 204.08, 68.60 and 50.93 µM, respectively), COX-1 (IC50 value of 287, 185, and 143 µM, respectively) and 5-LOX (IC50 value of 138, 50.76 and 20, 87 µM respectively). They exhibited choline-mimetic potential, such as compound 23, 31 and 44 inhibited AChE enzyme (IC50 value of 240, 174, and 134 µM, respectively) and BChE enzyme (IC50 value of 203, 134 and 97 µM, respectively). The Compounds 23, 31, 44 exhibited anti-diabetic effect via inhibiting α-amylase enzyme (IC50 values of 250, 106 and 60 µM, respectively). Molecular docking studies revealed that the synthesized compounds have good binding affinity in the binding pockets of AChE, BChE, COX-2, 5-LOX and α-amylase enzyme and showed high binding energies. The synthesized succinimide derivatives, i.e. compound 23, 31, 44 showed marked inhibitory activities against cyclooxygenase, lipoxygenase, α-amylase and cholinesterase enzymes. Among these three, compound 44 and 31 showed strong anti-inflammatory and anti-diabetic activity while they displayed moderate anti-cholinesterase activity supported by molecular docking results.Communicated by Ramaswamy H. Sarma.

Therapeutic potential of marine peptides in glioblastoma: Mechanistic insights.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in humans. It is characterized by excessive cell growth and accelerated intrusion of normal brain tissue along with a poor prognosis. The current standard of treatment, including surgical removal, radiation therapy, and chemotherapy, is largely ineffective, with high mortality and recurrence rates. As a result, traditional approaches have evolved to include new alternative remedies, such as natural compounds. Aquatic species provide a rich supply of possible drugs. The physiological effects of marine peptides in glioblastoma are mediated by a range of pathways, including apoptosis, microtubule balance disturbances, suppression of angiogenesis, cell migration/invasion, and cell viability; autophagy and metabolic enzymes downregulation. Herein, we address the efficacy of marine peptides as putative safe therapeutic agents for glioblastoma coupled with detail molecular mechanisms.