TRICHILIA EMETICA: ETHNOBOTANICAL SURVEY AND THE ANTITYROSINASE ACTIVITY RESULTS

African traditional medicine greatly contributes to the cosmetics industry. However scientific data confirming its use in improving post-inflammatory hyperpigmentation is sparse. Trichilia emetica is one of many medicinal plants used for dermatological purposes. Traditionally, the bark is used as part of a skin lightening treatment by Venda people (Limpopo Province). Tyrosinase is a multifunctional copper-containing enzyme that catalyzes tyrosine to form melanin which darkens the skin. In excess the process results in melanogenesis which promotes the formation of hyperpigmentation. An ethnobotanical survey was conducted by interviewing traditional healers and users. Trichilia emetica (methanol extracts, aqueous extracts of the bark and leaves) (20 – 200 µg/ml, pH 6.5) were tested in vitro using the colourimetric tyrosinase inhibition assay. Kojic acid and dimethyl sulfoxide were used as positive and negative controls, respectively. The results of the ethnobotanical survey showed that the powdered bark was mixed with lemon juice to reduce hyperpigmentation on the skin. Traditional healers reported that this paste has a skin-lightening effect and this was confirmed by the users of the treatment. The highest percentage inhibition on colourimetric tyrosinase assay was obtained with aqueous extract (12%) which was significantly lower than the positive control (98%). These studies confirmed that T. emetica has potential in reducing post-inflammatory hyperpigmentation, hence validating the use of the plant as a skin depigmenting remedy

Anti-aging potential of extracts from Sclerocarya birrea (A. Rich.) Hochst and its chemical profiling by UPLC-Q-TOF-MS

Abstract Background Degradation of components of the extracellular matrix such as elastin and collagen by elastase and collagenase accelerates skin aging. Phytochemicals that inhibit the activity of these enzymes can be developed as anti-aging ingredients. In this study, an investigation of the anti-aging properties of Sclerocarya birrea (A. Rich.) Hochst (Marula) extracts was conducted in vitro with the aim of developing chemically characterized anti-aging ingredients. Methods Marula stems, leaves and fruits were extracted using methanol:dichloromethane (DCM) (1:1). The stems were later extracted using acetone, ethanol, methanol:DCM (1:1) and sequentially using hexane, DCM, ethyl acetate and methanol. The stem ethanol extract was defatted and concentrated. Elastase and collagenase inhibition activities of these extracts and Marula oil were determined using spectrophotometric methods. The chemical profile of the ethanolic stem extract was developed using Ultra-performance-liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) with MassLynx software. Pure standards were used to confirm the identity of major compounds and were screened for anti-elastase and anti-collagenase activity. Results Marula stems extracts were the most active as they exhibited anti-elastase activity comparable to that of elafin (> 88%) and anti-collagenase activity as potent as EDTA (> 76%). The leaf extract had moderate anti-elastase activity (54%) but was inactive agains collagenase. Marula fruits and oil exhibited limited activity in both assays. The ethanolic extract of Marula stems was the most suitable based on its acceptability to the cosmetic industry and its anti-collagenase activity (99%). Defatting and concentration improved its antiaging activity and lowered the colour intensity. Six compounds have been tentatively identified in the chemical profile of the ethanolic extract of Marula stems of which four; quinic acid, catechin, epigallocatechin gallate and epicatechin gallate have been confirmed using pure standards. Epigallocatechin gallate and epicatechin gallate were as potent (p < 0.05) as EDTA at 5 μg/ml in the anti-collagenase assay. Conclusions The ethanolic extract of Marula stems can be developed into an anti-aging ingredient as it exhibited very good in vitro anti-aging activity and its chemical profile has been developed. Epicatechin gallate and epigallocatechin gallate contribute to the anti-aging activity of Marula stem ethanol extract

Macromolecular Antiproliferative Agents Featuring Dicarboxylato-Chelated Platinum

Cancerous diseases, together with cardiac afflictions, account for the predominant causes of death among the adult population of the Western world. The classical platinum drugs, with cisplatin as their parent, have established themselves for years as leading components in the oncologist’s arsenal of antitumor agents. As with most other antineoplastic drugs, however, incisive pharmacological deficiencies, notably excessive systemic toxicity and induction of drug resistance, have severely curtailed their overall efficaciousness. With the objective of overcoming these counterproductive deficiencies, the technique of polymer-drug conjugation, representing an advanced modality of drug delivery, has been developed in recent years to high standards worldwide. In a drug conjugate, water-soluble macromolecular carrier constructs designed in compliance with stringent pharmacological specifications are covalently, yet bioreversibly, interconnected with the bioactive agent. As a macromolecule following a pharmacokinetic pathway different from that of non-polymeric compounds, the conjugate acts as a pro-drug favorably transporting the agent through the various body compartments to, and into, the target cell, where the agent is enzymatically or hydrolytically separated from the carrier for its biological action. In the authors’ laboratories the conjugation strategy has been adopted as the primary tool for drug efficacy enhancement. The present paper describes a special type of platinum complex carrier-bound via dicarboxymetal chelation, synthesized from carboxyl-functionalized polyamide-type carriers by platination with trans-1,2-diaminocyclohexanediaquaplatinum(II) dinitrate. In a series of in vitro tests antiproliferative activities have been determined against several human cancer cell lines. Whereas no improvements are observed in tests against a colorectal cancer, outstanding findings of the screening program include a 10- to 100-fold increase in cell-killing performance of the conjugates relative to the (non-polymeric) cisplatin standard against the HeLa adenocarcinoma, and distinctly reduced resistance factors (again, relative to cisplatin) in tests against the A2780 and A2780-cis pair of ovarian cell lines. These findings augur well for future developments of this class of platinum drugs

Block Copolymer Micelles with Pendant Bifunctional Chelator for Platinum Drugs: Effect of Spacer Length on the Viability of Tumor Cells

Three monomers with 1,3-dicarboxylate functional groups but varying spacer lengths were synthesized via carbon Michael addition using malonate esters and ethylene- (MAETC), butylene- (MABTC), and hexylene (MAHTC) glycol dimethacrylate, respectively. Poly[oligo-(ethylene glycol) methylether methacrylate] (POEGMEMA) was prepared in the presence of a RAFT (reversible addition-fragmentation chain transfer) agent, followed by chain extension with the prepared monomers to generate three different block copolymers (BP-E80, BP-B82, and BP-H79) with similar numbers of repeating units, but various spacer lengths as distinguishing features. Conjugation with platinum drugs created macromolecular platinum drugs resembling carboplatin. The amphiphilic natures of these Pt-containing block copolymers led to the formation micelles in solution. The rate of drug release of all micelles was similar, but a noticeable difference was the increasing stability of the micelle against dissociation with increasing spacer length. The platinum conjugated polymer showed high activity against A549, OVCAR3, and SKOV3 cancer cell lines exceeding the activity of carboplatin, but only the micelle based on the longest spacer had IC50 values as low as cisplatin. Cellular uptake studies identified a better micelle uptake with increasing micelle stability as a possible reason for lower IC50 values. The clonogenic assay revealed that micelles loaded with platinum drugs, in contrast to low molecular weight carboplatin, have not only better activity within the frame of a 72 h cell viability study, but also display a longer lasting effect by preventing the colony formation A549 for more than 10 days