Muhammad Majid

Ethnomedicinal plant use value in the Lakki Marwat District of Pakistan

AIM OF THE STUDY Medicinal plants are regional treasures for the treatment of many ailments. The present research investigated and documented knowledge of indigenous commonly used medicinal plants, including traditional names, preparations and uses, in the Lakki Marwat District of Pakistan. The information gathered was statistically analyzed using the ICF method to establish baseline data for more comprehensive investigations of bioactive compounds of indigenous medicinal plants. MATERIALS AND METHODS Direct interviews of 78 informants were conducted during 2013-2014 to identify the preparations and uses of indigenous medicinal plants. Data were analyzed using various quantitative tools, such as use value, factor informant consensus and fidelity level. RESULTS A total of 62 species of flowering plants belonging to 34 families and 57 genera were reportedly used as ethnomedicines in the study area. Fabaceae, Brassicaceae, Apocynaceae, Solanaceae, Apiaceae, Poaceae, Zygophyllaceae, Asteraceae and Euphorbiaceae were the main plant families that comprised ethnobotanically important plant species. Traditional healers most frequently used aerial parts of plants. The following medicinal species were the most important in the present study with the highest use values (UV): Plantago ovata Forsk.(F. Plantaginaceae), Lawsonia inermis L.(F. Lythraceae), Calotropis procera (Aiton) Dryand.(F. Apocynaceae), Peganum harmala L.(F. Zygophyllaceae), Fagonia indica Burm.f. (F. Zygophyllaceae), Carthamus oxyacantha M.Bieb. (F. Asteraceae), Datura metel L. (F. Solanaceae) and Eruca vesicaria (L.) Cav. (F. Brassicaceae). Respiratory, otic, gastrointestinal and neurological ailments were the main categories that were classified as per factor informant consensus (Fic). The greatest number of species was used to cure gastrointestinal and andrological/gynecological problems. The highest fidelity level (Fl=100%) was achieved by Plantago ovata Forsk. (F. Plantaginaceae) to cure cardiovascular disorders. CONCLUSION The results of present study reveal that this enormous wealth of medicinal plants played an important role in the health care of the villagers in the study area. In addition, species with high use values (UV) might provide valuable leads for further pharmacological investigations.

In vitro and in vivo evaluation of anti-arthritic, antioxidant efficacy of fucoidan from Undaria pinnatifida (Harvey) Suringar

Seaweed and their constituents have been traditionally employed for the management of various human pathologic conditions such as edema, urinary disorders and inflammatory anomalies. The current study was performed to investigate the antioxidant and anti-arthritic effects of fucoidan from Undaria pinnatifida. A noteworthy in vitro antioxidant potential at 500μg/ml in 2, 2-diphenyl-1-picrylhydrazyl scavenging assay (80% inhibition), nitrogen oxide inhibition assay (71.83%), hydroxyl scavenging assay (71.92%), iron chelating assay (73.55%) and a substantial ascorbic acid equivalent reducing power (399.35μg/mg ascorbic acid equivalent) and total antioxidant capacity (402.29μg/mg AAE) suggested fucoidan a good antioxidant agent. Down regulation of COX-2 expression in rabbit articular chondrocytes in a dose (0-100μg) and time (0-48h) dependent manner, unveiled its in vitro anti-inflammatory significance. In vivo carrageenan induced inflammatory rat model demonstrated a 68.19% inhibition of inflammation whereas an inflammation inhibition potential of 79.38% was recorded in anti-arthritic complete Freunds adjuvant-induced arthritic rat model. A substantial ameliorating effect on altered hematological and biochemical parameters in arthritic rats was also observed. Therefore, findings of the present study prospects fucoidan as a potential antioxidant that can effectively abrogate oxidative stress, edema and arthritis-mediated inflammation and mechanistic studies are recommended for observed activities.

Quercus dilatata Lindl. ex Royle ameliorates BPA induced hepatotoxicity in Sprague Dawley rats

Quercus dilatata Lindl. ex Royle was evaluated for in vitro polyphenol content and antioxidant potential as well as in vivo protective role against bisphenol A (BPA) induced hepatotoxicity. The distilled water-acetone (QDDAE) and methanol-ethyl acetate (QDMEtE) extracts were standardized and administered in high (300 mg/kg body weight (BW) and low (150 mg/kg BW) doses to Sprague Dawley rats, injected with BPA (25 mg/kg BW). Silymarin (50 mg/kg BW) was used as positive control. Subsequently, blood and liver homogenates were collected after four weeks of treatment, and the defensive effects of both extracts against oxidative damage and genotoxicity were assessed via hematological and biochemical investigations, determination of endogenous expression of enzymes as well as levels of free radicals and comet assay. Between the two extracts, maximum phenolics (213 ± 0.15 μg gallic acid equivalent/mg dry extract (DE) and flavonoids (55.6 ± 0.16 μg quercetin equivalent/mg DE) content, DPPH scavenging activity (IC50: 8.1 ± 0.5 μg/ml), antioxidant capacity (53.7 ± 0.98 μg ascorbic acid equivalent (AAE)/mg DE) and reducing potential (228.4 ± 2.4 μg AAE/mg DE) were observed in QDMEtE. In in vivo analysis, a dose dependent hepatoprotective activity was exhibited by both the extracts. QDDAE demonstrated maximum reduction in levels of alanine transaminase (49.77 ± 3.83 U/l), thiobarbituric acid reactant substances (33.46 ± 0.70 nM/min/mg protein), hydrogen peroxide (18.08 ± 0.01 ng/mg tissue) and nitrite (55.64 ± 1.79 μM/ml), along with decline in erythrocyte sedimentation rate (4.13 ± 0.072 mm/h), histopathological injuries and DNA damage in BPA intoxicated rats as compared with QDMEtE. Likewise, QDDAE also significantly restored activity levels of endogenous antioxidants, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (POD) and GSH with values of 6.46 ± 0.15 U/mg protein, 6.87 ± 0.1 U/min, 11.94 ± 0.17 U/min and 16.86 ± 1.56 nM/min/mg protein, respectively. Comparative results were obtained for QDMEtE. In conclusion, the present study endorses the significant hepatoprotective potential of standardized extracts of Q. dilatata with known polyphenolics content and validates the traditional use of this plant in natural medicine to manage disorders like hepatotoxicity.

Protective aptitude of Periploca hydaspidis Falc against CCl4 induced hepatotoxicity in experimental rats

In the present study the antioxidant capacity of Periploca hydaspidis was assessed through various in vitro assays and by the hepatoprotective potential on CCl4 induced toxicity in rat. Phytochemical analysis of different extracts of P. hydaspidis indicated existence of various phytochemical classes. HPLC-DAD analysis of methanol extract indicated the existence of rutin, gallic acid and caffeic acid. Total phenolic (TPC) and total flavonoid content (TFC) exhibited significant (p < 0.05) correlation with 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide, hydroxyl ion, inhibition of β-carotene oxidation, iron chelation, reducing power and total antioxidant capacity. In hepatic sample of rat, CCl4 administration increased (p < 0.05) the level of nitrite, hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) whereas a decline was recorded in antioxidant enzymes; superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and in reduced glutathione (GSH). Concentration of alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) and globulin increased (p < 0.05) whereas level of total protein and albumin decreased in serum of CCl4 treated rats. Level of pro-inflammatory cytokines; tumor necrosis factor-α (TNF-α), tumor growth factor-β1 (TGF-β1) and resistin was increased (p < 0.05) in serum whereby anti-inflammatory markers; interleukin-10 (IL-10), adiponectin and nuclear factor erythroid 2- related factor 2 (Nrf-2) decreased (p < 0.05) in hepatic tissues of CCl4 treated rats. DNA damages and histopathological alterations were induced with administration of CCl4 to rat. The altered levels of various parameters provoked by CCl4 toxicity restored towards the control level by the methanol extract of P. hydaspidis in a dose dependent manner. These results suggested the presence of antioxidant and anti-inflammatory phyto-constituents in methanol extract of P. hydaspidis.

In vitro antioxidant efficacy and the therapeutic potential of Wendlandia heynei (Schult.) Santapau & Merchant against bisphenol A-induced hepatotoxicity in rats

The aim of present study was to access the antioxidant and ameliorative efficacy of Wendlandia heynei stem barks crude methanol extract (WHBM) against bisphenol A (BPA)-induced hepatotoxicity in the rat moel. WHBM and its derived fractions exhibited promising activity for the scavenging of DPPH, hydroxyl and nitrite radicals, iron chelation, and for the inhibition of β-carotene oxidation. The administration of BPA to Sprague Dawley rats (25 mg kg-1) for 28 days resulted in an elevated (p < 0.01) level of aspartate transaminase, alanine transaminase, alkaline phosphatase, and globulin, and at the same time a decrease (p < 0.01) in the level of total protein and albumin in the serum of the rats. In hepatic samples, the levels of catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, and reduced glutathione were decreased (p < 0.05), whereas thiobarbituric acid reactive substances, hydrogen peroxide, and the nitrite content were increased (p < 0.05) with BPA treatment to the rats. The administration of WHBM to BPA-intoxicated rats restored the altered levels of these parameters toward the control animals. Histopathological alterations of the hepatic tissues induced with BPA were restored with WHBM co-treatment to the rats. HPLC-DAD analysis ensured the occurrence of rutin, catechin, and caffeic acid in WHBM and WHBE. The results of this study suggested that the presence of phenolics and flavonoids in W. heynei bark might be responsible for it exhibiting antioxidant potential during the in vitro and in vivo studies and hence it has potential to be used as a therapeutic agent against oxidative stress associated diseases.

Nummularic acid, a triterpenoid, from the medicinal plant Fraxinus xanthoxyloides, induces energy crisis to suppress growth of prostate cancer cells

We recently identified and characterized nummularic acid (NA) as a major chemical constituent of Fraxinus xanthoxyloides, a medicinal plant used for over hundred years in traditional medicine. In this study, we describe its potential anti‐cancer activity using prostate cancer (PCa) cells as a model. We found that NA treatment (5‐60 μM) significantly reduced the proliferation and colony formation capabilities of PCa DU145 and C4‐2 cells in a time and dose dependent manner, reduced the migratory and invasive properties and increased apoptotic cell population. Mechanistically, we found that NA treatment to PCa cells resulted in a sustained activation of adenosine monophosphate‐activated protein kinase (AMPK). NA simultaneously increased acetyl CoA carboxylase phosphorylation and decreased pS6 phosphorylation, the two major substrates of AMPK. Further, NA treatment significantly elevated the cellular ADP/ATP ratio and altered glycolytic rate. We further observed a reversible decrease in oxygen consumption rate in NA treated cells when compared to the control. Finally, we performed global untargeted metabolomics which showed that NA treatment alters PCa cell metabolism at multiple sites including glycolysis, tricarboxylic acid, and glutamine metabolism which supported our observation of a possible AMPK activation. In summary, we report NA as a novel small molecule activator of AMPK that alters cellular metabolism to induce energy crisis and ultimately cancer cell death. Because of its unique mechanism NA could be potentially applicable against other cancer types.