Antioxidant, carbonic anhydrase inhibition and diuretic activity of Leptadenia pyrotechnica Forssk. Decne.

Background: Leptadenia pyrotechnica Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of L. pyrotechnica in nephrolithiasis, kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of L. pyrotechnica as diuretic. Methods: The 70 % methanolic L. pyrotechnica (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition. Results: Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10-300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways. Conclusion: L. pyrotechnica contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways.

Anti-inflammatory, anti-nociceptive and anti-pyretic activities of Cenchrus ciliaris L.

ETHNOPHARMACOLOGICAL RELEVANCE: Cenchrus ciliaris L. belongs to the family Poaceae and is found all over the world. It is native to the Cholistan desert of Pakistan where it is locally known as 'Dhaman'. Owing to high nutritional value, C. ciliaris is used as fodder while seeds are used for bread making which are consumed by locals. It also possesses medicinal value and is extensively employed to treat pain, inflammation, urinary tract infection, and tumors. AIM OF STUDY: Studies on the pharmacological activities of C. ciliaris are scarce in spite of its several traditional uses. To the best of our knowledge, no comprehensive study has been conducted on anti-inflammatory, analgesic and anti-pyretic activity of C. ciliaris until now. Here we employed an integrative phytochemical and in - vivo framework to evaluate the potential biological activities of C. ciliaris against inflammation, nociception and pyrexia experimentally induced in rodents. MATERIAL AND METHODS: C. ciliaris was collected from the desert of Cholistan, Bahawalpur, Pakistan. Phytochemical profiling of C. ciliaris was done by employing GC-MS analysis. Anti-inflammatory activity of plant extract was initially determined by various in - vitro assays including albumin denaturation assay and RBC membrane stabilization assays. Finally, rodents were utilized to evaluate in - vivo anti-inflammatory, antipyretic and anti-nociceptive activities. RESULTS: Our data revealed the presence of 67 phytochemicals in methanolic extract of C. ciliaris. The methanolic extract of C. ciliaris provided RBC membrane stabilization by 65.89 ± 0.32% and protection against albumin denaturation by 71.91 ± 3.42% at 1 mg/ml concentration. In in - vivo acute inflammatory models, C. ciliaris exhibited 70.33 ± 1.03, 62.09 ± 8.98, 70.24 ± 0.95% anti-inflammatory activity at concentration of 300 mg/ml against carrageenan, histamine and serotonin induced inflammation. In CFA induced arthritis, inhibition of inflammation was found to be 48.85 ± 5.11% at 300 mg/ml dose after 28 days of treatment. In anti-nociceptive assays C. ciliaris exhibited significant analgesic activity in both peripheral and centrally mediated pain. The C. ciliaris also reduced the temperature by 75.26 ± 1.41% in yeast induced pyrexia. CONCLUSION: C. ciliaris exhibited anti-inflammatory effect against acute and chronic inflammation. It also showed significant anti-nociceptive and anti-pyretic activity which endorses its traditional use in the management of pain and inflammatory disorders.

Antioxidant and Gastroprotective Activity of Suaeda fruticosa Forssk. Ex J.F.Gmel.

Suaeda fruticosa Forssk. Ex J.F.Gmel is traditionally used for inflammatory and digestive disorders, as a carminative, and for diarrhea. This plant is widely distributed in Asia, Africa, and the Mediterranean region. Aqueous methanolic extract of S. fruticosa (Sf.Cr) was prepared and screened for phytoconstituents through qualitative and GC-MS analysis. Quantification of total phenolic and flavonoid contents was performed, while antioxidant capacity was determined by DPPH, CUPRAC, FRAP, and ABTS assays. The gastroprotective activity was assessed in an ethanol-induced ulcer model. Gastric secretory parameters and macroscopic ulcerated lesions were analyzed and scored for ulcer severity. After scoring, histopathology was performed, and gastric mucus contents were determined. Oral pre-treatment of Sf.Cr demonstrated significant gastroprotection. The gastric ulcer severity score and ulcer index were reduced while the %-inhibition of ulcer was increased dose-dependently. The Sf.Cr significantly elevated the pH of gastric juice, while a decrease in total acidity and gastric juice volume was observed. Histopathology demonstrated less oedema and neutrophil infiltration in gastric mucosa of rats pre-treated with the Sf.Cr in comparison to ethanol-intoxicated animals. Furthermore, the gastric mucus contents were increased as determined by alcian blue binding. Sf.Cr showed marked gastroprotective activity, which can be attributed to antioxidant, antisecretory, and cytoprotective effects.

Verapamil attenuates oxidative stress and inflammatory responses in cigarette smoke (CS)-induced murine models of acute lung injury and CSE-stimulated RAW 264.7 macrophages via inhibiting the NF-κB pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), severe form of ALI, are characterized by overwhelming of lung inflammation, and no treatment is currently available to treat ALI/ARDS. Cigarette smoke (CS) is one of the prime causes to induce ALI/ARDS via oxidative stress. Despite extensive research, no appropriate therapy is currently available to treat ALI/ARDS. Hence, new potential approaches are needed to treat ALI/ARDS. Consequently, this project was designed to explore the protective effects of verapamil against CS-induced ALI by in vivo and in vitro method. In vivo data obtained from respiratory mechanics, pulmonary morphometric analyses and lung histopathology revealed that verapamil dose-dependently and strikingly decreased the lung weight coefficient, attenuated the albumin exudation into lungs, minimized the infiltration of macrophages and neutrophils into lungs, reduced the pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and keratinocyte chemoattractant (KC)) production, and improved the hypoxemia and lung histopathological changes. Similarly, verapamil also reduced the production of TNF-α, IL-6 and KC from cigarette smoke extract (CSE)-stimulated RAW 264.7 macrophage. Importantly, verapamil dose-dependently and remarkably suppressed the CS-induced oxidative stress via not only reducing the myeloperoxidase (MPO) activity of lungs, total oxidative stress (TOS) and malondialdehyde (MDA) content in the lungs and supernatant of RAW 264.7 macrophage but also improving total antioxidant capacity (TAC) and superoxide dismutase (SOD) production. Finally, verapamil strikingly decreased the NF-κB expression both in in vivo and in vitro models. Hence, verapamil has positive therapeutic effects against CS-induced ALI via suppressing uncontrolled inflammatory response, oxidative stress and NF-κB p65 signaling.

Revamping of Chronic Respiratory Diseases in Low- and Middle-Income Countries.

Low- and middle-income countries (LMICs) endure an asymmetrically high burden of worldwide disease and death caused by chronic respiratory diseases (CRDs), i.e., asthma, emphysema, bronchiectasis, and post-tuberculosis lung disease (PTLD). CRDs are firmly related with indigence, infectious diseases, and other non-communicable diseases (NCDs) and add to complex multi-disease with great impact on the lives and livelihood of those affected. The pertinence of CRDs to health and demographic wellbeing is relied upon to increment in the long time ahead, as expectations of life rise and the contending dangers of right on time youth mortality and irresistible infections level. The WHO has distinguished the counteraction and control of NCDs as an earnest improvement issue and crucial for the sustainable development goals (SDSs) by 2030. In this review, we center on CRDs in LMICs. We examine the early life roots of CRDs, challenges in their avoidance, identification and administration in LMICs, and the pathways to resolve for accomplish valid widespread wellbeing inclusion.

ANTIOXIDANT, ANTIBACTERIAL AND GUT MODULATING ACTIVITIES OF KALANCHOE LACINIATA.

Kalanchoe laciniata (L.) DC. (Crassulaceae) is a widely distributed plant in Africa and Asia. Traditionally, various communities use this plant for the treatment of a variety of ailments such as gut prob- lems, allergic conditions and wounds. The current study was designed to explore the antibacterial, antioxidant and gut modulating activities of K. laciniata in order to provide scientific rationale for its traditional uses. Phytochemical compounds were assessed through screening 70% crude methanolic extract of K. laciniata. Its gut modulatory activity was evaluated by in vitro tissue experiments on rabbit jejunum which yielded maximal spasmogenic response of 28.4 ± 4.6% (n = 4) at 3 mg/mL, while spasmolytic response was recorded with EC50 value of 3.2 mg/mL (2.8-3.5, 95% CI, n = 5). In antibacterial assays crude extract was found effective against Stapllococcus aurus and Bacillus subtilis, with MIC value of 5 and 2.5 mg/mL, respectively. The testing of the methanolic crude extract for antioxidants resulted in total phenolic contents of 27.8 ± 1.8 mg GAE/g DW and 22.7 ± 2.1 mg AAE/g DW total antioxidant activity. It also scavenged 17.3 ± 3.0% of DPPH free radical when compared with quercitin.