Taxifolin stability: In silico prediction and in vitro degradation with HPLC-UV/UPLC-ESI-MS monitoring.

Taxifolin has a plethora of therapeutic activities and is currently isolated from the stem bark of the tree Larix gmelinni (Dahurian larch). It is a flavonoid of high commercial interest for its use in supplements or in antioxidant-rich functional foods. However, its poor stability and low bioavailability hinder the use of flavonoid in nutritional or pharmaceutical formulations. In this work, taxifolin isolated from the seeds of Mimusops balata, was evaluated by in silico stability prediction studies and in vitro forced degradation studies (acid and alkaline hydrolysis, oxidation, visible/UV radiation, dry/humid heating) monitored by high performance liquid chromatography with ultraviolet detection (HPLC-UV) and ultrahigh performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS). The in silico stability prediction studies indicated the most susceptible regions in the molecule to nucleophilic and electrophilic attacks, as well as the sites susceptible to oxidation. The in vitro forced degradation tests were in agreement with the in silico stability prediction, indicating that taxifolin is extremely unstable (class 1) under alkaline hydrolysis. In addition, taxifolin thermal degradation was increased by humidity. On the other hand, with respect to photosensitivity, taxifolin can be classified as class 4 (stable). Moreover, the alkaline degradation products were characterized by UPLC-ESI-MS/MS as dimers of taxifolin. These results enabled an understanding of the intrinsic lability of taxifolin, contributing to the development of stability-indicating methods, and of appropriate drug release systems, with the aims of preserving its stability and improving its bioavailability.

The hydroethanolic Litchi chinensis leaf extract alleviate hepatic injury induced by carbon tetrachloride (CCl4) through inhibition of hepatic inflammation.

Various medicinal plants are traditionally used in a hepatoprotective manner, like, for example, the Litchi chinensis leaf infusion that is employed in Chinese medicine as liver tonics to strengthen hepatic functioning. In this context, the present study was designed to evaluate the hepatoprotective and acute toxicological effects of hydroethanolic L. chinensis leaf extract in HepG2 cells and mice. Specifically, the cytotoxicity and hepatoprotective activities of L. chinensis leaf extract were evaluated in HepG2 cells and in vivo against carbon tetrachloride (CCl4)-induced acute liver injury. The administration of CCl4 in mice provokes cell swelling, loss of sinusoid capillary spaces and structural disarrangement of the hepatic lobe, apoptosis and leukocyte infiltration. Further, CCl4 evokes an increase in serum alanine aminotransferase (ALT), tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in hepatic tissue. However, Silymarin, the positive control, and the L. chinensis extract were able to restore the viability of cells treated with CCl4 at all concentrations evaluated, reduced the inflammatory parameters, TNF and IL-6, reestablished hepatic tissue morphology and did not induce acute toxicological alterations. The data obtained underscore that the extract from L. chinensis leaves features hepatoprotective activity, corroborating with ethnopharmacological use, and does not lead to acute toxicological effects.

Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) relieved nociception and inflammation in mice - A topical herbal medicine against effects due to cnidarian venom-skin contact.

ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea pes-caprae is known as bayhops, beach morning glory or goat's foot, and in Brazil as salsa-de-praia. Its leaves are used in worldwide folk medicine for the relief of jellyfish-stings symptoms. The literature only reports the neutralizing effects of nonpolar plant derived over jellyfish venoms, without validating the popular use or exploring the mechanism of action. AIM OF THE STUDY: This study aimed to evaluate and validate the topical effects of a semisolid containing hydroethanolic extract obtained from the aerial parts of I. pes-caprae using different models of paw- and ear-oedema and spontaneous nociception in mice, attempting to better understand the mechanism involved in its effect. MATERIALS AND METHODS: Leaf and stem of I. pes-caprae were extracted by ethanol 50% (v/v) and the soft-extract was incorporated in Hostacerin® cream base at 0.5%, 1.0% and 2% (w/w). The anti-hypersensitivity effects were evaluated by injecting the Physalia physalis venom into the right mice's hindpaw pre-treated either with the semisolid containing the I. pes-caprae extract or with the isolated majority compound 3,5-Di-O-caffeoylquinic acid (ISA). The topical anti-inflammatory activity was investigated using both preclinical models: paw oedema induced by trypsin, bradykinin (BK), histamine and carrageenan, and ear oedema induced by capsaicin. Additionally, the model of spontaneous nociception induced by trypsin and capsaicin were used to verify the topical antinociceptive activity. RESULTS: The animals pre-treated with the semisolid containing I. pes-caprae extract or with the intraplantar injection of the major component (ISA) had the mechanical hypersensitivity induced by P. physalis venom significantly reduced. Significant inhibition was also observed in paw-oedema induced by trypsin, histamine and BK, and in a less extent in carrageenan-induced paw oedema. Similar effect was observed in mice challenged to the capsaicin-induced ear-oedema. Besides the vascular effects, the extract interfered with leukocyte migration induced by histamine injection. Finally, the semisolid presented significant inhibition in trypsin- and capsaicin-induced spontaneous nociception. CONCLUSIONS: The hydroethanolic extract of I. pes-caprae showed compliance with the topical popular use of the herbal product to relieve the symptoms evoked by the cnidarian venom-skin contact, such as neurogenic oedema and nociception. The extract components seem to interfere with the effects resulting from the TRPV1, B2R and PAR-2 activation, once it interfered with painful-behaviour and oedema induced by capsaicin, BK and trypsin, pointing the histaminergic system as the main target, once it is an important mediator in the signalling pathway of the aforementioned receptors.

Topical anti-inflammatory activity of semisolid containing standardized Aleurites moluccana L. Willd (Euphorbiaceae) leaves extract.

ETHNOPHARMMACOLOGICAL RELEVANCE: Aleurites moluccana is a medicinal plant popularly used to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general. Recently, pre-clinical studies have demonstrated that the dry extract obtained from A. moluccana leaves was effective as analgesic, anti-inflammatory and wound healing. AIM: The present study has aimed to evaluate the mechanisms involved in the topical anti-inflammatory effects of the semisolid containing 10mg/g of A. moluccana dried extract. MATERIAL AND METHODS: Ear edema induced by croton oil (2.5%) in mice was used throughout the study. The level of cytokines tumour necrosis factor (TNF) and interleukine-1ß (IL-1ß) and chemokine keratinocyte chemoattractant (CXCL1/KC), and neutrophil migration were quantified. The histological analysis has also been performed. RESULTS: The topical treatment with the semisolid was able to significantly inhibite the ear edema (35.77±7.35%). This effect was accompanied by the reduction of leukocyte migration, as well as TNF (53.75±12.96%), IL-1ß (38.36±5.92%), and CXCL1/KC (62.29±11.65%) decreased levels. CONCLUSIONS: This study demonstrated for the first time the mechanisms involved in the topical anti-inflammatory effect presented by the semisolid containing A. moluccana dried extract pointing as the main mechanism is the reduction in the leukocyte migration and consequently resulting in diminished levels of cytokins and chemokines, indicating this herbal product as a promissor anti-inflammatory phytomedicine to treat skin inflammatory diseases.