Anti-hemorrhoid activities from Cissus quadrangularis L.

Cissus quadrangularis L. is a medicinal plant widely used in Thai traditional medicine, especially to alleviate hemorrhoids. The aim of the present study was to investigate acute oral toxicity, anti-inflammatory and venoconstrictive effects of a whole plant standardized ethanol extract from C. quadrangularis in rats, followed by the evaluation of safety and efficacy of enteric film coated tablets containing the extract. The extract was standardized toquercetin as a biomarker for quality control of the extract and the tablets. In a 14-day acute oral toxicity study, the extract at dose levels up to 5000 mg kg^-1 body weight in rats did not cause signs of intoxication, death or gross pathological lesions. In the anti-inflammatory evaluation, the extract exhibited 50% inhibition of the carrageenan-induced rat paw edema at a dose of 500 mg kg^-1 after 5 h, which was nearly equivalent to the reference diclofenac at 10 mg 
kg^-1. The extract showed a venoconstrictive effect with EC₅₀ values of 0.01 and 0.03 µg mL^-1 for endothelium intact and denuded rat veins, respectively. The extract at a dose level of 1 µg mL^-1 exhibited approximately 78% of the venoconstriction of phenylephrine (10^-6 M). The subchronic toxicity test of enteric film coated tablets developed from the extract at the maximum dose of 5000 mg kg^-1 bodyweight did not result in treatment-related abnormalities in clinical observations and biological parameters when the control group was compared. In addition, there were no other gross and histopathological changes in vital organs. Based on the results of this study, enteric film coated tablets developed from the standardized extract of C. quadrangularis at the highest dose (5000 mg kg^-1 bodyweight) did not cause adverse effects. A double-blind randomized controlled clinical study in 160 hemorrhoid patients revealed that the enteric film coated tablets (200 mg twice day^-1) were effective in the treatment of bleeding, pain and prolapse of hemorrhoidal tissue with no statistical significant differences compared with the reference Cyclo 3 Fort drug. The extract is considered relatively safe and effective in the conservative treatment of hemorrhoids.