Bergenia pacumbis from Nepal, an astonishing enzymes inhibitor.

BACKGROUND: The Bergenia species are perennial herbs native to central Asia, and one of the most promising medicinal plants of the family Saxifragaceae which are popularly known as 'Pashanbheda'. The aim of this study was to evaluate antioxidant and α-amylase, α-glucosidase, lipase, tyrosinase, elastase, and cholinesterases inhibition potential of Bergenia pacumbis of Nepali origin collected from the Karnali region of Nepal. METHODS: The sequential crude extracts were made in hexane, ethyl acetate, methanol, and water. Antioxidant activities were analyzed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The α-amylase, α-glucosidase, lipase, tyrosinase, elastase, acetylcholinesterase, and butyrylcholinesterase inhibition were analyzed by the 3,5-Dinitrosalicylic acid (DNSA), p-Nitrophenyl-α-D-glucopyranoside (p-NPG), 4-nitrophenyl butyrate (p-NPB), l-3,4-dihydroxyphenylalanine (L-DOPA), N-Succinyl-Ala-Ala-p-nitroanilide (AAAPVN), acetylthiocholine, and butyrylcholine as a respective substrate. The major metabolites were identified by high performance liquid chromatography with electron spray ionization- quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) profiling. RESULTS: Our results revealed the great antioxidant ability of crude extract of B. pacumbis in ethyl acetate extract against both DPPH (IC50 = 30.14 ± 0.14 µg/mL) and ABTS (IC50 = 17.38 ± 1.12 µg/mL). However, the crude methanol extract of B. pacumbis showed the comparable enzymes inhibitions with standard drugs; α-amylase (IC50 = 14.03 ± 0.04 µg/mL), α-glucosidase (IC50 = 0.29 ± 0.00 µg/mL), lipase (IC50 = 67.26 ± 0.17 µg/mL), tyrosinase (IC50 = 58.25 ± 1.63 µg/mL), elastase (IC50 = 74.00 ± 3.03 µg/mL), acetylcholinesterase (IC50 = 31.52 ± 0.58 µg/mL), and butyrylcholinesterase (IC50 = 11.69 ± 0.14 µg/mL). On the basis of HPLC-ESI-QTOF-MS profiling of metabolites, we identified major compounds such as Bergenin, Catechin, Arbutin, Gallic acid, Protocatechuic acid, Syringic acid, Hyperoside, Afzelechin, Methyl gallate, Paashaanolactone, Astilbin, Quercetin, Kaempferol-7-O-glucoside, Diosmetin, Phloretin, and Morin in methanol extract which has reported beneficial bioactivities. CONCLUSION: Our study provides a plethora of scientific evidence that the crude extracts of B. pacumbis from Nepalese origin in different extracting solvents have shown significant potential on inhibiting free radicals as well as enzymes involved in digestion, skin related problems, and neurological disorders compared with the commercially available drugs.

LC-ESI-QTOF-MS for the Profiling of the Metabolites and in Vitro Enzymes Inhibition Activity of Bryophyllum pinnatum and Oxalis corniculata Collected from Ramechhap District of Nepal.

The objective of this study was to profile the chemical components and biological activity analysis of crude extract of Bryophyllum pinnatum and Oxalis corniculata. Results revealed that the analyzed plant materials encompass the high amount of total phenolic and flavonoids content and have significant antioxidant activities. Furthermore, methanol extracts are the potential source of α-amylase, α-glucosidase, lipase, tyrosinase and elastase inhibitors. High resolution mass spectrometry revealed the presence of diverse metabolites such as quercetin 3-O-α-L-rhamnopyranoside, myricetin 3-rhamnoside, bersaldegenin 1,3,5-orthoacetate, bryophyllin C, syringic acid, caffeic acid, p-coumaric acid, and quercetin in B. pinnatum and isoorientin, swertisin, apigenin 7,4'-diglucoside, vitexin, 4-hydroxybenzoic acid, vanillic acid, ethyl gallate, 3,3',4'-trihydroxy-5,7-dimethoxyflavone, and diosmetin-7-O-ß-D-glucopyranoside in O. corniculata. Our finding suggested that these two plant species have high medicinal importance and are potential source of inhibitors for modern pharmaceuticals, nutraceuticals and cosmetics industries.

Shiga Toxin Mediated Neurologic Changes in Murine Model of Disease.

Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli, and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed. Microglial cell responses to neural injury include up-regulation of surface-marker expression (e.g., Iba1) and stereotypical morphological changes. Mice injected with Stx2a showed increased Iba1 staining, mild morphological changes associated with microglial activation (thickening of processes), and increased microglial staining per unit area. Microglial changes were observed in the cortex, hippocampus, and amygdala regions, but not the nucleus. Magnetic resonance imaging (MRI) of Stx2a-treated mice revealed no hyper-intensities in the brain, although magnetic resonance spectroscopy (MRS) revealed significantly decreased levels of phosphocreatine in the thalamus. Less dramatic changes were observed following Stx1 challenge. Neither immortalized microvascular endothelial cells from the cerebral cortex of mice (bEnd.3) nor primary human brain microvascular endothelial cells were found to be susceptible to Stx1 or Stx2a. The lack of susceptibility to Stx for both cell types correlated with an absence of receptor expression. These studies indicate Stx causes subtle, but identifiable changes in the mouse brain.