Cryptolepine, an indoloquinoline alkaloid, in the management of diabetes mellitus and its associated complications

Abstract

Background:Effective long-term management is the key to treatment of diabetes mellitus (DM) and its complications.Aim:To ascertain the ability of cryptolepine (CRP) in managing DM and some associated complications.Materials and Methods:Changes in fasting blood sugar (FBS), body weight, response to thermally-induced pain, and semen quality were assessed in normal and alloxan-induced diabetic rats treated with CRP (10, 30, or 100 mg/kg), glibenclamide (10 mg/kg), or normal saline (2 ml/kg) per os. Hematological profile, liver and kidney function tests, lipid profile, as well as liver, kidney, and pancreas histopathological examinations were also conducted to establish possible effects of CRP treatment.Results:CRP treatment reduced (P ≤ 0.001) FBS and body weight, inhibited (P ≤ 0.05 - 0.001) the latency to tail flick or withdrawal from pain stimulus. It did not alter (P > 0.05): Hematological parameters, elevated (P ≤ 0.05 - 0.001) plasma aspartate transaminase, alanine transaminase, and gamma-glutamyl transferase, reduced (P ≤ 0.01) plasma urea, and elevated (P ≤ 0.001) plasma creatinine associated with DM. CRP, however, reversed (P ≤ 0.05 - 0.001) DM-associated elevation (P ≤ 0.05 - 0.001) of plasma cholesterol, triglycerides, and low-density lipoproteins, and the reduction in high-density lipoproteins. CRP (10-30 mg/kg) showed dose-dependent regeneration of β-islet cells but could not repair degenerated liver and kidney tissue. CRP worsens dose-dependently (P ≤ 0.001) reduced sperm quality associated with DM.Conclusion:CRP abolishes hyperglycemia, weight loss, cold allodynia, neuropathic pain, and hyperlipidemia as well as pancreatic β-islet cell damage associated with DM. It, however, does not improve liver and kidney damage and lowered semen quality.

Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei

“…Cryptolepis sanguinolenta (Apocynaceae) and Xylopia aethiopica (Annonaceae) are two medicinal plants commonly used by Ghanaian herbal practitioners to treat malaria [ 3 , 4 ]. Cryptolepine, the indoquinoline alkaloidal constituent of Cryptolepis sanguinolenta has been reported to be responsible for the anti-hyperglycaemic [ 5 , 6 ], anti-inflammatory [ 7 ], antibacterial [ 8 ] and antiplasmodial [ 9 , 10 ] activities of the plant. In the unripe fruits of Xylopia aethiopica , the kaurene diterpene, xylopic acid, which occurs as the major constituent has been reported to possess antipyretic and anti-malarial [ 11 ], analgesic [ 12 , 13 ] and anti-depressant [ 14 ] properties among others.…”

Phytochemical and Pharmacological Review of Cryptolepis sanguinolenta (Lindl.) Schlechter

“…The antifertility effect of C. sanguinolenta has also been demonstrated by Ameyaw et al [ 90 ] and Akhigbe et al [ 89 ]. These studies provide evidence that supports the hypothesis that C. sanguinolenta extract significantly suppresses sperm count.…”

“…To evaluate the relevance of cryptolepine, the major alkaloid of C. sanguinolenta in the long-term management of diabetes mellitus, Ameyaw et al [ 90 ] examined the effect of the alkaloid in alloxan-induced diabetes. Cryptolepine treatment significantly ( p ≤ 0.001) reduced fasting blood glucose and body weight and inhibited the latency to withdrawal from pain stimulus.…”

“…Regeneration of pancreatic β -islet cells by the alkaloid is very important in the management of diabetes mellitus. Cryptolepine, however, does not improve liver and kidney damage [ 90 ].…”

“…Treatment with cryptolepine, the major alkaloid of C. sanguinolenta , resulted in a further increase in the elevated levels of plasma aspartate transaminase associated with induction of diabetes mellitus in Sprague-Dawley rats. However, no significant effects on elevated levels of alanine transaminase and gamma-glutamyl transferase were observed [ 90 ]. However, in the absence of any disease, administration of the plant extract resulted in no changes in serum transaminases, suggesting the plants' limited effect on the liver [ 88 ].…”