Antinociceptive Synergism of Pomegranate Peel Extract and Acetylsalicylic Acid in an Animal Pain Model.

Several modern drugs, which are derived from traditional herbal medicine are used in contemporary pharmacotherapy. Currently, the study of drug-plant interactions in pain has increased in recent years, looking for greater efficacy of the drug and reduce side effects. The antinociception induced by intragastric co-administration of the combination of pomegranate peel extract (PoPEx) and acetylsalicylic acid (ASA) was assessed using the isobolographic analysis in formalin test (nociceptive and inflammatory pain). The effective dose that produced 30% of antinociception (ED30) was calculated for both drugs from the logarithmic dose-response curves, subsequently generating a curve with the combination on fixed proportions (1:1) of PoPEx and ASA. Through isobolographic analysis, this experimental ED30 was compared with the calculated theoretical additive ED30. The result was a synergistic interaction, the experimental ED30 was significantly smaller (p < 0.05) than the theoretical ED30. The antinociceptive mechanism of the PoPEx-ASA combination involves the l-Arginine/NO/cGMP pathway, antioxidant capacity, and high content of total phenols. These findings suggest that an interaction between PoPEx and ASA could be a novel treatment for inflammatory and nociceptive pain, also diminish the secondary reactions of ASA.

Pomegranate as a Potential Alternative of Pain Management: A Review.

The use of complementary medicine has recently increased in an attempt to find effective alternative therapies that reduce the adverse effects of drugs. Punica granatum L. (pomegranate) has been used in traditional medicine for different kinds of pain. This review aims to explore the scientific evidence about the antinociceptive effect of pomegranate. A selection of original scientific articles that accomplished the inclusion criteria was carried out. It was found that different parts of pomegranate showed an antinociceptive effect; this effect can be due mainly by the presence of polyphenols, flavonoids, or fatty acids. It is suggested in the literature that the mechanisms of action may be related to the activation of the L-arginine / NO pathway, members of the TRP superfamily (TRPA1 or TRPV1) and the opioid system. The implications for the field are to know the mechanisms of action by which this effect is generated and thus be able to create alternative treatments for specific types of pain, which help alleviate it and reduce the adverse effects produced by drugs. The results propose that pomegranate and secondary metabolites could be considered in the treatment of inflammatory, nociceptive, and neuropathic pain.

Promising Antioxidant Activity of Erythrina Genus: An Alternative Treatment for Inflammatory Pain?

The negative impact that oxidative stress has on health is currently known. The complex mechanism of free radicals initiates a series of chain reactions that contribute to the evolution or development of different degenerative disorders. Likewise, these disorders are usually accompanied by inflammatory processes and, therefore, pain. In this sense, reactive oxygen species (ROS) have been shown to promote the nociceptive process, but effective treatment of pain and inflammation still represents a challenge. Over time, it has been learned that there is no single way to relieve pain, and as long as there are no other alternatives, the trend will continue to apply multidisciplinary management, such as promote the traditional use of the Erythrina genus to manage pain and inflammation. In this sense, the Erythrina genus produces a wide range of secondary metabolites, including flavanones, isoflavones, isoflavones, and pterocarpans; these compounds are characterized by their antioxidant activity. Phenolic compounds have demonstrated their ability to suppress pro-oxidants and inhibit inflammatory signaling pathways such as MAPK, AP1, and NFκB. Although there is preclinical evidence supporting its use, the pharmacological effect mechanisms are not entirely clear. Nowadays, there is a fast advancement in knowledge of the disciplines related to drug discovery, but most of nature's medicinal potential has not yet been harnessed. This review analyzes the decisive role that the Erythrina genus could play in managing inflammatory pain mediated by its compounds and its uses as an antioxidant.

Antioxidant and Hepatoprotective Effects of Croton hypoleucus Extract in an Induced-Necrosis Model in Rats.

The aim of this study was to evaluate the antioxidant and hepatoprotective activity of Croton hypoleucus (EC). The present work reports the first pharmacological, toxicological, and antioxidant studies of EC extract on liver injury. Liver necrosis was induced by thioacetamide (TAA). Five groups were established: Croton Extract (EC), thioacetamide (TAA), Croton extract with thioacetamide (EC + TAA), vitamin E with thioacetamide (VE + TAA) and the positive control and vehicle (CT). For EC and EC + TAA, Wistar rats (n = 8) were intragastrically pre-administered for 4 days with EC (300 mg/kg.day) and on the last day, EC + TAA received a single dose of TAA (400 mg/kg). At 24 h after damage induction, animals were sacrificed. In vitro activity and gene expression of superoxide dismutase (SOD), catalase (Cat), and Nrf2 nuclear factor were measured. The results show that EC has medium antioxidant properties, with an IC50 of 0.63 mg/mL and a ferric-reducing power of 279.8 µM/mg. Additionally, EC reduced hepatic damage markers at 24 h after TAA intoxication; also, it increased SOD and Cat gene expression against TAA by controlling antioxidant defense levels. Our findings demonstrated the hepatoprotective effect of EC by reducing hepatic damage markers and controlling antioxidant defense levels. Further studies are necessary to identify the mechanism of this protection.

Future therapeutic targets for the treatment and prevention of cholesterol gallstones.

The formation of cholesterol gallstones involves very complex imbalances, such as alterations in the secretion of biliary lipids (which involves the ABCG5, ABCG8, ABCB4 and ABCB11 transporters), biochemical and immunological reactions in the gallbladder that produce biliary sludge (mucins), physicochemical changes in the structure of cholesterol (crystallization), alterations in gallbladder motility, changes in the intestinal absorption of cholesterol (ABCG5/8 transporters and Niemann-Pick C1L1 protein) and alterations in small intestine motility. Some of these proteins have been studied at the clinical and experimental levels, but more research is required. In this review, we discuss the results of studies on some molecules involved in the pathophysiology of gallstones that may be future therapeutic targets to prevent the development of this disease, and possible sites for treatment based mainly on the absorption of intestinal cholesterol (Niemann-Pick C1L1 and ABCG5/8 proteins).

Antinociceptive and anti-inflammatory activities of Geranium bellum and its isolated compounds.

BACKGROUND: Geranium bellum Rose, locally known as "Pata de león", is a perennial plant distributed in the mountains of Hidalgo, Mexico. It is widely used in Mexican traditional medicine to treat fever, pain, and gastrointestinal disorders. To date, there are not published studies regarding the in vivo antinociceptive and anti-inflammatory potential of the acetone-aqueous extract from the aerial parts of G. bellum. METHODS: Antinociceptive effects of the acetone-aqueous G. bellum (AGB) extract and the isolated compounds were assessed using experimental pain models, including thermal nociception like hot plate test, and chemical nociception induced by intraperitoneal acetic acid or subplantar formalin injection in vivo. The anti-inflammatory properties of the extract were studied using systemic administration in carrageenan-induced paw edema. RESULTS: Intra-gastric administration of AGB (75, 150, and 300 mg/kg) showed a dose-dependent antinociceptive effect in intraperitoneal acetic acid (writhing), thermal nociception in CD1 mice, and subplantar formalin models, as well as anti-inflammatory effect in carrageenan- induced paw edema in Wistar rats. Geraniin and quercetin showed the highest antinociceptive activity in writhing test, whereas ellagic acid was the most active compound in the hot plate model. CONCLUSION: These studies provide evidences that G. bellum shows antinociceptive and anti- inflammatory effects, and gives support to its use in treating pain in Mexican traditional medicine.