Synthetic berberine derivatives as potential new drugs

Abstract The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential.

Green Synthesis of Silver Nanoparticles Using Parthenium Hysterophorus: Optimization, Characterization and In Vitro Therapeutic Evaluation.

Traditional synthetic techniques for silver nanoparticles synthesis involve toxic chemicals that are harmful to humans as well as the environment. The green chemistry method for nanoparticle synthesis is rapid, eco-friendly, and less toxic as compared to the traditional methods. In the present research, we synthesized silver nanoparticles employing a green chemistry approach from Parthenium hysterophorus leaf extract. The optimized parthenium silver nanoparticles (PrSNPs) had a mean particle size of 187.87 ± 4.89 nm with a narrow size distribution of 0.226 ± 0.009 and surface charge -34 ± 3.12 mV, respectively. The physicochemical characterization of optimized SNPs was done by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Moreover, the transmission electron microscopy (TEM) analysis indicates the spherical shape of NPs with an average diameter of 20-25 nm. PrSNPs were investigated for in vitro antibacterial, antifungal, anti-inflammatory, and antioxidant properties, and showed excellent profiles. The cytotoxic activity was analyzed against two cancer cell lines, i.e., B16F10 and HepG2 for 24 h and 48 h. PrSNPs proved to be an excellent anticancer agent. These PrSNPs were also employed for the treatment of wastewater by monitoring the E. coli count, and it turned out to be reduced by 58%; hence these NPs could be used for disinfecting water. Hence, we can propose that PrSNPs could be a suitable candidate as an antimicrobial, antioxidant, anti-inflammatory, and antitumor agent for the treatment of several ailments.

A New Oleanane Type Saponin from the Aerial Parts of Nigella sativa with Anti-Oxidant and Anti-Diabetic Potential.

Natural product studies explore potential and interesting new compounds to discover innovative drugs. Nigella sativa (N. sativa) (Ranunculaceae) is traditionally used to treat diabetes. Flavonoids and triterpenoid mostly show anti-diabetic activity. The current study aim to identify new compounds by a systematic study of the anti-oxidant and anti-diabetic activity of aerial parts of N. sativa concerning. Phytochemicals were isolated from the methanolic extract of aerial parts of the plant by column chromatography and identified by nuclear magnetic resonance spectroscopy and mass spectroscopy. A new triterpenoid saponin glycoside was isolated along with flavonoids. The anti-diabetic study was carried out by DPPH, ABTS, α -glucosidase, and protein tyrosine phosphatase 1B assays at doses of 12.5 to 250 µM. The isolated phytochemicals were identified as 3-O-(ß-d-xylopyranosyl-(1-3)-α-l-rhamnopyrnaosyl-(1-2)-α-l-arabinopyranosyl]-28-O-(α-l-rhamno-pyranosyl-(1-4)-ß-d-glucopyranosyl-(1-6)-ß-d-glucopyranosyl] hederagenin (1), flaccidoside III (2), catechol (3), quercetin-3-gentiobiosides (4), magnoflorine (5), nigelflavonoside B (6), nigelloside (7), quercetin sphorotrioside (8), kaempferol-3, 7-diglucoside (9), kaempferol 3-O-rutinoside (10), rutin (11), 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsylhederagenin (12), 3ß,23,28-trihydroxyolean-12-ene-3-O-α-l-arabinopyranoside(1→4)-a-rhamnopyranosyl,(1→4)-ß-d-gluco-pyranoside (13), 3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsyl]-28-O-ß-d-gluco-pyranosyl hederagenin (14), and α-hederin (15). These were isolated and are reported for the first time in this study. Compared 13 was identified as a new compound. Compound 2 was isolated for first time from the genus Nigella. Compound 6 was found to be the most active in the DPPH, and ABTS assays and compound 10 was found to be the most active in the α-glucosidase assay, with IC50 32.7 ± 0.1, 95.18 ± 0.9, 214.5 ± 0.0 µΜ, respectively. Compound 12, at a dose of 125 µΜ, showed anti-diabetic activity in a PTP1B assay with IC50 91.30 ± 2.5 µΜ. In conclusion, the anti-diabetic activity of N. sativa is due to its flavonoids and TTSGs. Therefore, our studies suggest that the aerial parts of N. sativa are also a valuable and alternate source of valuable phytochemicals that could be used to develop anti-oxidant and anti-diabetic medicines.

A Review of Medicinal Plants in Cardiovascular Disorders: Benefits and Risks.

Many cultivated and wild plants are used for the management of various diseases, specifically renal and hepatic diseases and those of the immune and cardiovascular systems. In China, medicinal plants from ancient to modern history have been used in patients with angina pectoris, congestive heart failure (CHF), systolic hypertension, arrhythmia, and venous insufficiency for centuries. The latest increase in the fame of natural products and alternative medicine has revived interest in conventional remedies that have been consumed in the management of CVD. The cardio-protective properties of the various herbs are possibly due to their anti-oxidative, antihypercholesterolemic, anti-ischemic activities, and inhibition of platelet aggregation that reduce the risk of CVD. Ethno-pharmacological and biological properties of these plants are explored, based upon published scientific literature. Although a majority of medicinal plants having a biological mechanism that linked with CVD management, to date, published literature pertaining to their promising scientific properties are still poorly understood. Compared with synthetic medicines, alternative medicines do not need scientific studies before their formal approval from the government sector and due to this purpose; their safety, as well as efficacy, still remain elusive. Taken together, we addressed all accessible evidence on alternative medicines commonly consumed in CVD management. Our comprehensive analysis of the scientific literature indicated that many TCMs are available and valuable herbal medication would be the best alternative for the management of CVD as a complementary therapy. Furthermore, practitioners should always discuss possible benefits-risks of alternative medicines with patients so that they are aware of the consumption of alternative medications.

Preparation of microemulsion containing Lycopersicon esculentum extract: In vitro characterization and stability studies.

Lycopene, the active component of Lycopersicon esculentum species, has been reported for the protecting capabilities against ultra-violet induced skin pigmentation, antioxygen and antityrosinase activities. In the present study, extract of tomato fruit was obtained from the Lycopersicon esculentum plant using solvent system comprised of hexaneethanol-acetone. The phyto chemical active constituent lycopene was then identified by spectrophotometric technique at 470nm. Micro emulsions were developed containing different ratio of water, isopropyl myristate (oil), tween 80 and propylene glycol as surfactant and co-surfactant respectively via pseudoternary phase diagram. Various physicochemical tests were performed including globular size, conductivity, viscosity, scanning electron microscopy (SEM), refractive index (RI) and pH measurement for the formulation characterization. Results of physical and chemical stability studies showed that the micro emulsion with proportion of surfactant: co-surfactant of 2:1 (Smix) was found to be optimized formulation and with enhanced stability. Therefore, concluded that the stability of the micro emulsion was dependent on the proportions of surfactant co-surfactant, water and oil in the preparation.