Prophylaxis and Treatment of Inflammation with Pentacyclic Chemotype of Uncaria tomentosa

Villegas Vilchez L.F.; Ascencios J.H.; Dooley T.P. · Integrative Medicine (Boulder) (2023)

Resumen

Context: Anti-inflammatory drugs and biologics can effectively treat inflammatory conditions and diseases but can also cause burdensome side effects. Many patients prefer to use time-tested, traditional medicinal products and dietary supplements, but such products seldom receive the rigorous testing required for regulatory approvals of drugs and biologics. Thus, it is advantageous to demonstrate by experimentation the pharmacological and toxicological properties of unapproved natural products and compared to benchmark approved drugs or biologics. Objective: The studies intended to evaluate Samento®, a commercial hydro-alcoholic extract of the pentacyclic chemotype of Uncaria Tomentosa (Willd.) DC, for the prophylactic and treatment effects of irritant-induced inflammation and antigen-induced arthritic inflammation in two rat models. The studies were also intended to create a clinical bridge rationale for the use of Samento® in the treatment of inflammation in humans, with a suggested allometrically scaled starting dose. Design: The research team performed two in vivo animal model studies of induced inflammation in rats. Setting: The studies took place at the Universidad Peruana Cayetano Heredia in Lima, Peru. Prophylaxis Model of Irritant-Induced Inflammation: Holtzman rats in five groups (five each per group) were administered 14 daily doses of Samento® at 250, 500, and 1000 mg/kg of wet weight, or 40 mg/kg of naproxen sodium as a positive control, or nothing as a negative control. At 14 days the right legs of the rats were challenged by injection into the connective tissue by the chemical irritant carrageenan. Two hours thereafter the weight of the irritant-injected right leg was compared to the non-injected left leg of each rat, to determine the level of irritant-induced inflammation. Treatment Model of Antigen-Induced Arthritic Inflammation: Arthritic inflammation was induced in five groups of Lewis rats (five each per group) by intradermal injection of the tail with non-allogeneic, bovine type II collage in incomplete Freund’s adjuvant. A sixth group was not injecte with collagen antigen as a non-induced control. Ten days afte the induction of arthritic inflammation in the five injecte groups, individual groups were treated with Samento® at 250 500, and 1000 mg/kg of wet weight daily for 21 days, or 0.2 mg kg of methotrexate twice per week as a positive control, o nothing as a negative control. At 21 days the animals wer assessed for antigen-induced arthritic inflammation an assigned an analog score ranging from 0 to 4. Results: The research team confirmed the presence o pentacyclic oxindoles and the absence of tetracyclic oxindole within Samento®. In the prophylactic model, 14 days o pretreatment with oral Samento® produced dose-dependent statistically significant reductions in inflammation in the rats leg weights between the carrageenan induction an postintervention, for the 250, 500, and 1000 mg/kg Samento groups (P<.05 for all groups). The 1000 mg/kg group had a 74% anti-inflammatory effect versus 97% with the 40 mg/kg o naproxen sodium in the positive control group. In the treatmen model, 21 days of oral administration of Samento® produce dose-dependent, statistically significant reductions in arthriti inflammation postintervention, for the 250, 500, and 1000 mg kg Samento® groups (P<.05 for all groups). Treatment with th highest tested dose of the extract (1000 mg/kg) yielded an 85% anti-inflammatory effect versus 90% with 0.2 mg/kg o methotrexate in the positive control group. Conclusions: The two rat models revealed that the Uncari phytotherapy Samento® was an effective prophylactic as wel as a treatment for induced inflammation in rats. The highes dose of the pentacyclic chemotype of Uncaria approached th anti-inflammatory activities of the established benchmar pharmaceutical positive controls. The results in the two ra models suggest an allometrically scaled starting dose o Samento® of 4 g daily in humans.

Instituciones: Universidad Peruana Cayetano Heredia