Syed Uzair Ali Shah

Anti-nociceptive, anti-inflammatory and sedative activities of the extracts and chemical constituents of Diospyros lotus L.

Diospyros lotus L. is traditionally used in various diseases including pain and sleep disorders. The pain and inflammation are the common problems, which are treated with various synthetic analgesic drugs, and associated the side effects. The natural products have gained significant importance over synthetic drugs. The importance of phyto-medicine the current study has been designed with the aim to investigate the analgesic and anti-inflammatory effects of Diospyros lotus and bioassay guided isolation from its crude fractions. Seven known compounds; lupeol (1), 7-methyljuglone (2), β-Sitosterol (3), stigmasterol (4) betulinic acid (5), diospyrin (6; DS) and 8-hydroxyisodiospyrin (7; HDS) which were hitherto unreported from D. lotus. The chloroform fraction (CFDL) and isolated compounds DS and HDS were evaluated for anti-nociceptive, sedative and anti-inflammatory effects. The acetic acid induced writing was significantly (p<0.001) protected by CFDL (72.43%), DS (40.87%) and HDS (65.76%) at higher doses which exhibited peripheral and central analgesic effects in acetic acid and hot-plat pain paradigms. Regarding the anti-inflammatory effect the CFDL (77.43%), DS (80.54%) and HDS (75.87%) protected the carrageenan paw edema after 3rd h. The central analgesic effect was significantly antagonized with naloxone (0.5 mg/kg), showing opiodergic mechanism of action. The CFDL, DS and HDS were also proved sedative in open field animal models. In acute toxicity study the chloroform fraction [CFDL (50, 100 and 150 mg/kg)], DS (5 and 10 mg/kg) and HDS (5 and 10 mg/kg) were found safe. Our study concluded that CFDL, DS and HDS have marked anti-nociceptive, anti-inflammatory and sedative effect. The anti-nociceptive and anti-inflammatory effects of the roots of D. lotus are partially attributed due to the presence of analgesic constituents like diospyrin (DS), 8-hydroxyisodiospyrin (HDS) and strongly supports the ethno-pharmacological uses of D. lotus as anti-nociceptive, anti-inflammatory and sedative.

N-(2-hydroxy phenyl) acetamide inhibits inflammation-related cytokines and ROS in adjuvant-induced arthritic (AIA) rats

The present study was carried out to study the anti-arthritic and anti-inflammatory activity of N-(2-hydroxy phenyl) acetamide in adjuvant-induced arthritis in adult female Sprague Dawley rats. During experimental period, body weight and paw oedema volume were observed. At the end of each experiment, plasma and serum samples were collected and used for estimation of pro-inflammatory cytokines IL-1 beta and TNF-alpha and oxidative stress markers i.e., nitric oxide, peroxide and GSH. Our results suggested that, the reduction in body weight and increase in paw oedema volume were significantly retarded in the AIA rats receiving 5mg/kg and 10mg/kg doses of N-(2-hydroxy phenyl) acetamide as compared to diseased control animals. The serum levels of IL-1 beta and TNF-alpha were reduced as compared to those in the diseased control group. Treatment with N-(2-hydroxy phenyl) acetamide also altered oxidative stress markers in relation to its anti-inflammatory activity. Based on our results, it can be concluded that N-(2-hydroxy phenyl) acetamide possesses promising anti-arthritic property.

A novel anticonvulsant modulates voltage‐gated sodium channel inactivation and prevents kindling‐induced seizures

Here, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch‐clamp electrophysiology assayed the activity of ISOX on voltage‐gated sodium channels (VGSCs) in both cultured neurons and brain slices isolated from controls and rats with experimental epilepsy (kindling model). Quantitative transcription polymerase chain reaction (qRT‐PCR) (QPCR) assessed brain‐derived neurotrophic factor (BDNF) mRNA expression in kindled rats, and kindled rats treated with ISOX. ISOX suppressed sodium current (INa) showing an IC50 value of 185 nM in cultured neurons. ISOX significantly slowed the recovery from inactivation (ISOX τ = 18.7 ms; Control τ = 9.4 ms; p < 0.001). ISOX also enhanced the development of inactivation by shifting the Boltzmann curve to more hyperpolarized potentials by −11.2 mV (p < 0.05). In naive and electrically kindled cortical neurons, the IC50 for sodium current block was identical to that found in cultured neurons. ISOX prevented kindled stage 5 seizures and decreased the enhanced BDNF mRNA expression that is normally associated with kindling (p < 0.05). Overall, our data show that ISOX is a potent inhibitor of VGSCs that stabilizes steady‐state inactivation while slowing recovery and enhancing inactivation development. Like many other sodium channel blocker anti‐epileptic drugs, the suppression of BDNF mRNA expression that usually occurs with kindling is likely a secondary outcome that nevertheless would suppress epileptogenesis. These data show a new class of anti‐seizure compound that inhibits sodium channel function and prevents the development of epileptic seizures.

Biological Evaluation and Docking Analysis of Daturaolone as Potential Cyclooxygenase Inhibitor

This study deals with the isolation of the active constituent(s) from a methanolic extract of Pistacia integerrima J. L. Stewart barks and it was also oriented to evaluate the in vivo and in silico anti-inflammatory activity. By NMR and crystallography techniques, we have isolated a triterpenoid identified as daturaolone (compound 1). This compound showed in vivo a significant and dose dependent (1–30 mg/kg) anti-inflammatory activity on carrageenan-induced mouse paw oedema (ED50 = 10.1 mg/kg) and on acetic acid-induced writhing responses in mice (ED50 = 13.8 mg/kg). In the in vivo experiments, the effect of tested compound was also evaluated in presence of the reference drug diclofenac (1–30 mg/kg). Moreover, in silico analysis of receptor ligand complex shows that compound 1 interacts with cyclooxygenases (COXs) binding sites displaying an interesting interaction with COX-1. These findings suggest that compound 1 isolated from P. integerrima possesses in vivo anti-inflammatory and antinociceptive potentials, which are supported in silico by an interaction with COXs receptors.

Synthesis of Anthranilic Acid and Phthalic Anhydride Ligand and theirMetal Complexes

Anthranilic acid and phthalic anhydrides have the ability make ligand complexes with the metal ions, which were found to be important for various applications. In the present study, the attempts were carried to form complexes of anthranilic acid and phthalic anhydride ligand with Lead acetate (Pb(CH3COO)2), Cobalt chloride (Cocl2. 6H2O), Cadmium sulfate (CdSO4·H2O), Copper chloride (CuCl2.2H20), and Tin chloride of well-defined stoichiometry in the range of pH 6 and 8 in variable ratios. The IR spectra of complexes were interpreted and compared with data in the literature. Furthermore the resultant complexes were evaluated for the anti-bacterial potential.

The Anti-Arthritic and Immune-Modulatory Effects of NHAG: A Novel Glucosamine Analogue in Adjuvant-Induced Arthritis

Rheumatoid arthritis (RA) is potentially devastating condition which lacks good treatment options. Pro-inflammatory cytokines interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and oxidative stress markers such as nitric oxide (NO) and peroxide (PO) are mediators of RA pathogenesis. In the present study N-[2,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-3-yl]acrylamide (NHAG), analogue of glucosamine, was evaluated in adjuvant-induced arthritic model of rats. The disease progression was monitored by analysing arthritis scoring, loss of body weight, paw oedema, and histological changes in joints. RA associated hyperalgesia was evaluated by gait analysis. The serum or plasma levels of NO, PO, glutathione (GSH) superoxide dismutase (SOD) IL-1β and TNF-α were analyzed to monitor the state of disease severity. The arthritic control animals exhibited significant increase in arthritic score (P < 0.003) and paw oedema (P < 0.001) with parallel loss in body weight (P < 0.04). The NHAG-treated arthritic animals exhibited refinement in the gait changes associated with arthritis. NHAG also significantly decreased the NO (P < 0.02) and PO (P < 0.03) with concurrent increased in GSH (P < 0.04) and SOD (P < 0.007). Both IL-1β (P < 0.001) and TNF-α (P < 0.001), were significantly decreased in NHAG-treated group. Thus NHAG might have a therapeutic potential for arthritis by exerting antioxidative and immunomodulatory effects.

In Vivo Study on Analgesic, Muscle-Relaxant, Sedative Activity of Extracts of Hypochaeris radicata and In Silico Evaluation of Certain Compounds Present in This Species

Background Hypochaeris radicata (flatweed) from the family Asteraceae is a medicinal plant found in Europe, Middle East, and India. In folkloric medication, it is used to heal jaundice, dyspepsia, constipation, rheumatism, and hypoglycemia as well as renal problems. Leaves and roots of the plant have antioxidant and antibacterial properties. The plant is a rich source of pharmacologically active phytochemicals; however, it is explored scantily. The objective of the current study was to identify the chemical composition and investigate the in vivo biological potency of crude extracts of this plant. Methods The crude extract and the fractions were screened for various phytochemical groups of constituents following standard procedures. The acute toxicity was assayed for safe range of dose determination. The analgesic potential of the extract and fractions was assessed by acetic acid-induced writhing test. The muscle-relaxant activity was examined by standard inclined-plane test and traction test. Sedative potential of extract/fractions was assessed by using standard white wood procedures. Furthermore, docking analysis of two compounds present in the ethyl acetate fraction of the plant was assessed against 3D cyclooxygenase-1 and -2 (COX-1 and COX-2). Results The extract/fractions of H. radicata showed significant analgesic effect in in vivo model of peripheral algesia. The docking analysis of previously isolated molecules from the plant also exhibited promising interaction with COX-1 and COX-2. Also, the plant has a mild sedative and muscle-relaxant potential. Thus, our study provided pharmacological rationale for the traditional uses of the plant as analgesic and anti-inflammatory remedy. Conclusion The crude extracts and fractions exhibited excellent activity due to active phytochemicals. These active phytochemicals also exhibited promising interaction with COX-1 and COX-2. These findings directed researcher to isolate active compounds from H. radicata which may be used as a potential source of active secondary metabolites.