Pharmacological Basis of Rumex hastatus D. Don in Gastrointestinal Diseases with Focusing Effects on H+/K+-ATPase, Calcium Channels Inhibition and PDE Mediated Signaling: Toxicological Evaluation on Vital Organs

Molecules. 2022 Sep 12;27(18):5919. doi: 10.3390/molecules27185919.

Abstract

This present study aimed to delineate Rumex hastatus D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti H. pylori, antiulcer effects, and toxicology. The preliminary phytochemical analysis of Rumex hastatus showed different phytoconstituents and shows different peaks in GC-MC chromatogram. Rumex hastatus crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50-300 mg/kg) protection (0-100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration-response curves (CRCs) to the right, Rh.Cr (0.3-1 mg/mL) and Rh.ETAC (0.1-0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti-H. pylori effect, also shows an inhibitory effect against H+/K+-ATPase. Rumex hastatus showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H+/K+-ATPase mRNA levels. Rumex hastatus was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H+/K+-ATPase pump and voltage-gated L-type calcium channel showed E-values of -8.7 and -9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results.

Keywords: H+/K+-ATPase; Rumex hastatus; anti-inflammatory; anti-ulcer; antioxidant; calcium channels.

MeSH terms

  • Adenosine Triphosphatases
  • Animals
  • Antidiarrheals / chemistry
  • Antioxidants / pharmacology
  • Calcium Channels, L-Type
  • Castor Oil
  • Charcoal / pharmacology
  • Cyclooxygenase 2
  • Gastrointestinal Diseases* / drug therapy
  • Isoproterenol / pharmacology
  • Jejunum
  • Mice
  • NF-kappa B / pharmacology
  • Parasympatholytics / pharmacology
  • Phytochemicals / pharmacology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • RNA, Messenger
  • Rabbits
  • Rats
  • Rumex* / chemistry
  • Rutin / pharmacology
  • Tumor Necrosis Factors
  • Verapamil / pharmacology

Substances

  • Adenosine Triphosphatases
  • Antidiarrheals
  • Antioxidants
  • Calcium Channels, L-Type
  • Castor Oil
  • Charcoal
  • Cyclooxygenase 2
  • Isoproterenol
  • NF-kappa B
  • Parasympatholytics
  • Phytochemicals
  • Plant Extracts
  • RNA, Messenger
  • Rutin
  • Tumor Necrosis Factors
  • Verapamil

Grants and funding

This research received no external funding.