Inhibition of a Myotoxic Phospholipase A2 isolated from Crotalus durissus cumanensis by Pentacyclic Triterpenes

Tue, 04 Mar 2025 00:00:00 -0500

BACKGROUND: Ophidian accidents have been recognized as public health events in Colombia since 2004 and have been systematically reported since 2007, constituting a significant public health problem. One of the components present in the venoms of Viperidae snakes is the phospholipase A₂ (PLA₂) enzyme, playing a fundamental role in snakebite poisoning and responsible for many of the local effects that are not neutralized by antivenoms, the only treatment approved for the management of these accidents. Traditional herbal treatments hold promise, with ethnopharmacological studies emphasizing compounds, particularly pentacyclic triterpenes, as potential inhibitors of PLA₂.
OBJECTIVE: To identify compounds with the potential to reduce or neutralize the local effects generated by PLA₂, present in the venom of snakes of the Viperidae family, the major cause of ophidian accidents in Colombia.
METHODS: Four triterpenic compounds (madecassic acid, ursolic acid, betulinic acid, and oleanolic acid) were evaluated to determine the inhibitory capacity on the enzymatic activity of myotoxic phospholipase A₂, extracted from Crotalus durissus cumanensis venom and purified by RP-HPLC. To determine the inhibitory capacity of the compounds against the enzymatic activity of PLA₂, the synthetic monodisperse substrate 4-nitro-3- (octanoloxy) benzoic acid was used. Molecular docking was also performed to identify by visual inspection the interactions between the compounds and the active site of the enzyme.
RESULTS: The highest percentage of inhibition was presented by ursolic acid (47.01%). This is supported by the results of the molecular docking, where this compound was found to have interactions with Leu2, Phe24, Tyr52, and Lys69, amino acids involved in the catalytic activity of the enzyme.
CONCLUSIONS: Ursolic acid was determined as the most promising compound among the four evaluated against the local effects generated by PLA₂. Future studies may be performed to determine other potential benefits of these compounds versus other biological actions of the enzyme.

Phoradendron bathyoryctum Eichler relieves acute nociceptive pain stimulus and carrageenan-induced inflammation in mice

Tue, 04 Mar 2025 00:00:00 -0500

Background: The genus Phoradendron belongs to the Santalaceae family and possesses several species with antitumor, cytotoxic, and immunomodulatory activity, where pain and inflammation are common symptoms. It is used in venereal and liver diseases in Paraguayan folk medicine. In addition, it claims to have tonic properties for the heart and central nervous system. Previous studies have shown that crude extract of Phoradendron bathyoryctum Eichler (Pb) has anxiolytic and antidepressant activity.
Objective: This work aimed to determine the anti-nociceptive and anti-inflammatory activity ofPb using acute models in mice.
Methods: the anti-nociceptive activity of Pb was evaluated using mechanical pressure (Randall-Selitto test), acetic acid (writhing test), and heat (hot plate test) noxious stimulus in mice. The anti-inflammatory activity was assessed through carrageenan-induced plantar edema in mice previously treated with Pb.
Results: Presences of high polarity alkaloids, steroids/ free triterpenoids, leucoanthocyanidins, and tannins were detected in phytochemical studies. Oral doses of 30 (p<0.01) and 300 (p<0.001) mg/kg of Pb denoted a significant dose-dependent increase in pain threshold, using the Randall-Selitto and Writhing test (30; p<0.05; and 300; p<0.01. In addition, consistent with the above anti-nociceptive effect, an increase in the reaction latency time after oral administration of Pb at a dose of 300 mg/kg (p<0.05) in the hot plate test was denoted. Finally, a significant reduction of edema (30 mg/kg; p<0.01) induced by 1% carrageenan was evidenced, demonstrating a potential anti-inflammatory activity of Pb compared to the positive edema control. Interestingly, the anti-edematous activity of Pb showed a similar intensity response compared to the group treated with 10 mg/kg indomethacin (p<0.01).
Conclusion: This work revealed that the crude extract of Pb can increase pain threshold, be compatible with an analgesic effect, and reduce edema (anti-inflammatory) induced by Carrageenan in mice. Further pharmacological and chemical studies are being conducted to elucidate molecular mechanisms and components involved in the observed effects.

Vitae

Inhibition of a Myotoxic Phospholipase A2 isolated from Crotalus durissus cumanensis by Pentacyclic Triterpenes

Phoradendron bathyoryctum Eichler relieves acute nociceptive pain stimulus and carrageenan-induced inflammation in mice