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Acrylamide (ACR) is widely used in industries. Oxidative stress and apoptosis pathways are important mechanisms behind ACR-induced hepatotoxicity and neurotoxicity. Regarding to antioxidant and antiapoptotic properties of punicalagin (PUN), the protective effect of this agent on ACR-induced toxicity in rat was evaluated. Rats were divided into seven groups: control, ACR (50 mg/kg/day, i.p.), PUN (10, 20, and 40 mg/kg/day, i.p.) plus ACR, vitamin E (200 mg/kg, i.p.) plus ACR, and PUN groups. After 11 days, the gait score test was evaluated. Then, the animals were sacrificed and the malondialdehyde (MDA) and glutathione (GSH) contents were determined in the brain and liver tissues. Apoptosis-involved factors and myelin basic protein (MBP) were determined by western blotting. Severe movement disorder, MDA enhancement, and GSH reduction in the brain and liver tissues were observed in ACR-treated animals. The Bax/Bcl2 ratio and caspase-3 levels were enhanced in the tested tissues. ACR elevated the level of aspartate aminotransferases and decreased serum protein and albumin concentration. PUN recovered movement disorders, changed the level of markers which are important in oxidative stress and reduced apoptosis. Also, PUN increased the MBP level which was reduced due to ACR toxicity. PUN can protect against ACR-induced toxicity through antioxidant and antiapoptotic properties.

Plant polyphenols are a potential source of new antimicrobial molecules against bacteria because most newly developed antimicrobial agents do not improve the clinical management of infectious diseases. The potential synergism between the major polyphenolic compounds present in a Cistus salviifolius extract, which was characterized by HPLC-ESI-MS/MS, was investigated by the isobole method and the fractional inhibitory concentration index determination. Pairwise combinations of selected flavonoids and ellagitannins present in C. salviifolius extract were assayed against the in vitro growth of Staphylococcus aureus. Some combinations revealed synergic effects, resulting in a reduction of the minimum inhibitory concentration required to inhibit 50% growth (MIC50) up to 20 times lower as compared with the individual compounds. Some of the combinations exhibited MIC50 values close to drug potency level (0.5–1 µg/mL). Punicalagin and myricetin were the major contributors in the combinations. The proportion between the compounds in the synergic mixtures is crucial and may explain the superior antimicrobial activity displayed by this extract when compared with other botanical extracts. The rational optimization of these combinations could lead to the design of potent antimicrobial phytopharmaceuticals, which may improve the performance of current antibiotics, taking advantage of the multi-targeted and synergic molecular interactions of selected polyphenols. Copyright © 2015 John Wiley & Sons, Ltd.

Two exploratory clinical studies investigating proprietary pomegranate products showed a trend of effectiveness in increasing prostate-specific antigen doubling time in patients with prostate cancer. A recent clinical study did not support these results. We therefore analysed a lot of the marketed pomegranate blend for co-active pomegranate compounds. The high-performance liquid chromatography method was used to detect punicalagin, ellagic acid and anthocyanins. Total polyphenoles were determined by the Folin-Ciocalteu method using gallic acid as reference. The results show that the co-active compounds in the daily dose of the pomegranate blend were far below those previously tested and that the photometric assessment is not reliable for the standardisation of study medications. Not pomegranate but the low amount of co-active compounds in the proprietary pomegranate blend was responsible for its clinical ineffectiveness. Copyright © 2014 John Wiley & Sons, Ltd.

Fifteen crude extracts prepared from seven Ethiopian medicinal plants used to treat various infectious diseases were assessed for their ability to inhibit the growth of Mycobacterium tuberculosis. A preliminary screening of the crude extracts against M. tuberculosis typus humanus (ATCC 27294) was done by dilution assay using Lowenstein-Jensen medium. None of the tested extracts except the acetone fraction obtained from the stem bark of Combretum molle (R. Br. ex G. Don.) Engl & Diels (Combretaceae) showed significant inhibitory action against this strain. The acetone fraction of the stem bark of C. molle caused complete inhibition at concentrations higher than 1 mg/mL. Phytochemical analysis of the bioactive fraction led to the isolation of a major tannin and two oleanane-type pentacyclic triterpene glycosides. The tannin was identified as the ellagitannin, punicalagin, whilst the saponins were characterized as arjunglucoside (also called 4-epi-sericoside) and sericoside. All the pure compounds were further tested against the ATCC strain. Punicalagin was found to inhibit totally growth of the ATCC and also of a patient strain, which was fully sensitive to the standard antituberculosis drugs, at concentrations higher than 600 microg/mL and 1.2 mg/mL, respectively. On the other hand, the saponins failed to show any action on the ATCC strain. It appears that our findings are the first report of tannins exhibiting antimycobacterial activity.

Punicalagin and punicalin were isolated from the leaves of Terminalia catappa L., a Combretaceous plant distributed throughout tropical and subtropical beaches, which is used for the treatment of dermatitis and hepatitis. Our previous studies showed that both of these compounds exert antioxidative activity. In this study, the antihepatotoxic activity of punicalagin and punicalin on acetaminophen-induced toxicity in the rat liver was evaluated. After evaluating the changes of several biochemical functions in serum, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased by acetaminophen administration and reduced by punicalagin and punicalin. Histological changes around the hepatic central vein and oxidative damage induced by acetaminophen were also recovered by both compounds. The data show that both punicalagin and punicalin exert antihepatotoxic activity, but treatment with larger doses enhanced liver damage. These results suggest that even if punicalagin and punicalin have antioxidant activity at small doses, treatment with larger doses will possibly induce some cell toxicities.

Punicalagain, an active principle isolated from the leaves of Lumnitzera racemosa (Combretaceae), reversed the fall in arterial blood pressure in conscious Wistar rats with orthostatic hypotension induced by injection of hexamethonium into animals subjected to 90° head-up tilts for 60 s. Punicalagin was found to be less effective on prazosin-induced orthostatic hypotension. Plasma norepinephrine (NE) was elevated by intravenous injection of punicalagin in a dose-dependent manner from 0.5 to 15 mg/kg, both in normotensive rats and the orthostatic hypotensive animals. An increase of mean blood pressure was also found in rats that received the injection of punicalagin; this increase in blood pressure was totally abolished by prazosin. Failure of hexamethonium or pentolinium, antagonists of ganglionic nicotinic receptors, to influence the NE releasing action of punicalagin ruled out the participation of ganglionic stimulation. This NE-releasing action of punicalagin was, however, totally blocked by the inhibitors of noradrenergic nerve terminals, guanethidine or bretylium. Also, the activity of punicalagin was not modified by adrenalectomy. Thus, a direct release of NE from the noradrenergic nerve terminals by punicalagin seems responsible for the reversal of orthostatic hypotension.