A new anti-inflammatory lupane in Ziziphus jujuba (L.) Gaertn. var. hysudrica Edgew.

Objectives: To investigate extracts of the stem bark of Ziziphus jujuba (L.) Gaertn. var. hysudrica Edgew. (Rhamnaceae) for anti-inflammatory activity and isolate the active principle(s). Methods: The dry powder was macerated separately in three types of solvents to prepare methanol extract (ME), ethyl acetate extract (EE), and chloroform extract (CE). Following in vitro anti-inflammatory screening, the most active extract was selected to isolate the active compound. Both, the active extract and isolated compound were further tested on rats using the carrageenan-induced inflammation model. The blood and paw tissue were subjected to qPCR, and histopathology, respectively. Key findings: CE showed comparatively higher anti-inflammatory activity (85.0-95.0 %) in all in vitro assays, except the heat-induced membrane stabilization model (p < 0.05), and upon column chromatography, it yielded a pure crystalline compound. The compound was a pentacyclic triterpenoid (Lupane), named as hydroxymethyl (3ß)-3-methyl-lup-20(29)-en-28-oate (Hussainate). CE (500 mg/kg) and Hussainate (1.0 mg/kg) reduced edema in 5 h after carrageenan administration. The activity of Hussainate was found to be comparable to that of dexamethasone (standard). The possible activity mechanism was the downregulation of tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-II), NF-κB, and IL-1ß. Conclusions: This study reveals that chloroform extract of the stem's bark of Z. jujuba may be used to prepare standardized anti-inflammatory herbal products using Hussainate as an active analytical marker. Hussainate may be used as a lead to develop anti-inflammatory drugs.

Design, synthesis, biological evaluation and molecular docking studies of quinoline-anthranilic acid hybrids as potent anti-inflammatory drugs.

Despite the high global prevalence, rheumatoid arthritis lacks a satisfactory treatment. Hence, the present study is undertaken to design and synthesize novel anti-inflammatory compounds. For this, quinoline and anthranilic acid, two medicinally-privileged moieties, were linked by pharmacophore hybridization, and following their computational assessments, three hybrids 5a-c were synthesized in good over all yields. The in vitro and in vivo anti-inflammatory potential of these hybrids was determined by anti-denaturation and anti-proteinase, and carrageenan-induced paw edema models. The computational studies of these hybrids revealed their drug-likeness, optimum pharmacokinetics, and less toxicity. Moreover, they demonstrated high binding affinity (-9.4 to -10.6 kcal mol-1) and suitable binding interactions for TNF-α, FLAP, and COX-II. A three-step synthetic route resulted in the hybrids 5a-c with 83-86% yield of final step. At 50 µg mL-1, the antiprotease and anti-denaturation activity of compound 5b was significantly higher than 5a and 5c. Furthermore, 5b significantly reduced the edema in the right paw of the rats that received carrageenan. The results of this study indicate the medicinal worth of the novel hybrids in treating inflammatory disorders such as rheumatoid arthritis.

Microscopic, phytochemical and antibacterial studies of Zizyphus oxyphylla Edgew. leaves.

Microscopic, phytochemical and pharmacological profiles are required for correct identification of a plant material to ensure consistent efficacy and safety. But such data are not available for the leaf of an important medicinal plant, Zizyphus oxyphylla Edgew. (Family: Rhamnaceae). Therefore, the current study aimed to investigate leaves of the plant for microscopic, phytochemical and antibacterial studies. Powdered material was subjected to microscopy, proximate analyses and estimation of total primary metabolites. Then, different types of extracts prepared using various solvents in order of increasing polarity were screened for antibacterial activity against seven standard strains. The most active extract was hydrolyzed and aglycone enriched fraction was extracted and screened for antibacterial activity. The powder microscopy indicated the presence of vascular bundles filled with cuboidal calcium oxalate crystals, anisocytic stomata and xylary vessels with reticulate and scalariform thickenings. Proximate features and primary metabolites provided characteristic identifying patterns. The most active extract (methanol) upon acidic hydrolysis exhibited higher activity against B. bronchiseptica (26.01±0.01 mm), S. aureus (26.00±0.00 mm), P. aeruginosa (24.03±0.02 mm) and M. luteus (24.02± 0.00 mm). The results of the current study provide identifying microscopic and phytochemical profiles that may be useful for correct identification of leaves of the plant. Aglycone enriched extract is having remarkable antibacterial activity hence may be used for activity-guided isolation.