Innovative Delivery Systems for Curcumin: Exploring Nanosized and Conventional Formulations.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nanodelivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nanoencapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nanoencapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nanoencapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes

Pharmacological Role of Biosynthetic Products

A product such as hydrated carbons (carbohydrates), lipids, proteins, and nucleic acids play significant roles in plants metabolically. But there are other natural organic products manufactured by plants, some of the products are complex molecules, which are not primary metabolites. These biosynthetic products have possesses a variety of therapeutic merits in drug discovery. Some biosynthetic products show numerous appreciable therapeutic effects making them beneficial for trimming down polypharmacy and as viable candidates for the management of chronic diseases such as diabetes and hypertension in patients. The chapter discusses the pharmacological role of some biosynthetic products from plants and animals

Methanolic extract of Nauclea diderrichii (stem-bark) show anti-microbial, anti-oxidant and anti-inflammatory bioactivities

The aqueous stem-bark extract of the tropical plant Nauclea diderrichii is used in ethnomedicine to manage symptoms of rheumatism through minimally examined mechanisms. The objective of the study is to examine the scientific bases for the ethnomedicinal use of the plant for the management of rheumatism. As part of this effort to explain its ethnomedicinal efficacy, this study compared and contrasted the anti-microbial, anti-oxidant and anti-inflammatory activities of the methanolic extract with that of the diethylether extract. Broth dilution assay, DPPH radical scavenging assay and carrageenan-induced foot swelling of 7-day old chicks were utilized for the experimental assessment of the bioactivities of Nauclea diderrichii. Polar methanolic extract exhibited a higher antioxidant status in vitro as estimated quantitative differences in total phenolic content, in total antioxidant capacity and in DPPH and H2O2 radical scavenging converged to show the methanolic extract as a more potent anti-oxidant. The methanolic extract also possess better in vivo anti-inflammatory activity as demonstrated by the 1.5-fold lower ED50 relative to that of the diethylether. The methanolic extract demonstrated better broad-spectrum anti-microbial activity against a panel of six clinical isolates of bacterial and fungi pathogens in vitro. The relative strength of the bioactivities of the methanolic extract derives from a higher slew of phytochemical content that is a 3-fold difference larger. The results of this study support the beneficial effect of Nauclea diderrichii in its continuing ethnomedicinal use to target rheumatism chemotherapeutically

Macaranga barteri stem bark extract exerts anti-inflammatory and anti-hyperalgesia activity in murine models

This study was undertaken to evaluate the anti-inflammatory, anti-hyperalgesia and antioxidant activity of the hydro-alcoholic stem bark extract of Macaranga barteri (MBE). The carrageenan-induced foot oedema and Hargreaves thermal hyperalgesia models in rats were used to examine the anti-inflammatory and anti-hyperalgesic effects respectively. The 2, 2-diphenyl-2-picrylhydrazyl hydrate (DPPH) free radical scavenging and total antioxidant capacity assays were used to determine the antioxidant activity. In a curative protocol, MBE (30, 100, 300 mg kg-1, p.o.) dose dependently and significantly inhibited carrageenan-induced foot oedema by 37.01 ± 13.08, 53.01 ± 9.87 and 64.11 ± 9.05% respectively (ED50 = 89.37 ± 7.52 mg kg-1). The extract further attenuated cutaneous hyperalgesia by prolonging paw withdrawal latencies towards an external heat stimulus with an ED50 of 105.5 ± 4.22 mg kg-1. MBE was found to possess a total antioxidant capacity of 531.62 ± 10.98 mg g-1 dry weight (Gallic acid equivalent) and scavenged DPPH free radicals with an IC50 of 19.45 ± 1.46 µg/mL. The results provide the first report on the anti-inflammatory, analgesic and antioxidant activity of M. barteri stem bark and partly justify its traditional use in the management of inflammation and pain. This could be attributed to phytochemicals such as tannins, terpenoids, sterols, coumarins and flavonoids which were identified in preliminary phytochemical studies of the stem bark

Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment.

CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors

Co-extract mixture from Strophanthus hispidus (roots) and Aframomum meleguta (seeds) show phytochemical synergy in its anti-inflammatory activity

Background: Combination of extracts from multiple plants are typically used in ethnomedicine to putatively offer more potent chemotherapeutic and chemopreventive effects than that of individual extracts from single plants. Aqueous extracts from two multipurpose plants Strophanthus hispidus (roots) and Aframomum meleguta (seeds) are topically co-administered in the nasal cavities for the ethnomedicinal management of chronic sinusitis. Aim: This study assessed the potential phytochemical synergy between constituent extracts of Strophanthus hispidus (roots) and Aframomum meleguta (seeds) in its anti-inflammation, anti-microbial and anti-oxidant effects. Methods and Materials: Broth dilution assay assessed anti-microbial activities. DPPH radical scavenging assay examined the scope of anti-oxidant activities and inhibition of carrageenan-induced 7-day old chick feet oedema revealed anti-inflammatory activities. Results: Anti-microbial activities of individual plant extracts in broth dilution assay showed comparable potency to that of the co-extract mixture. Similarly, individual extracts showed levels of DPPH radical scavenging activities in anti-oxidant assay that was comparable to those found for the co-extract mixture. In contrast to these two effects, inhibition of carrageenan-induced 7-day old chick feet oedema revealed an anti-inflammatory activity evoked by co-extract mixtures that was greater than the sum of the individual potencies of the two extracts. Conclusion: The potential phytochemical synergy of the two plants extracts in its anti-inflammatory response largely validates ethnomedicinal practice and generally confirms growing literature reports that ascribe the net pharmacological activities of herbal extracts to the combined multi-activities of unique phytochemical entities at multiple target sites

The Effectiveness of Varying Combination Ratios of A. cordifolia and M. indica against Field and Laboratory Strains of P. falciparum In Vitro

Background. Drug resistance in malaria is a global problem, with reports of Plasmodium parasites resistant to the current first-line antimalarial drug, artemisinin, expanding from Southeast Asia to Africa. There is therefore an urgent need to identify new drug candidates that will be effective against the existing malaria parasites. Drug combination therapy presents a myriad of advantages over monotherapy including delayed onset of resistance, potentiation, and synergism. This present study explored the effectiveness of combinations of aqueous extracts of Alchornea cordifolia (A. cordifolia) and Mangifera indica (M. indica) at clearing both laboratory and field isolates of P. falciparum. Methods. Synchronized ring stage cultures of field (FA08) and laboratory strains (NF54 and CamWT_C580Y) of P. falciparum were subjected to combinations of different concentrations and ratios of aqueous extracts of A. cordifolia and M. indica. The growth inhibition of the individual plant extracts and their combinatory effects were studied in vitro using SYBR Green I drug assay. Results. The A. cordifolia extract exhibited 50% inhibitory concentration (IC50) of 2.71, 7.80, and 3.56 μg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Mangifera indica exhibited IC50 of 18.11, 20.08, and 10.23 μg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Additive, synergistic and antagonistic interactions were observed at different combinations of A. cordifolia and M. indica extracts. Conclusion. A combination product containing A. cordifolia and M. indica has the potential to serve as an effective antimalarial as majority of the tested combinations of aqueous extracts of A. cordifolia and M. indica extracts exhibited synergistic effects in vitro against the NF54, CamWT_C580Y, and FA08 P. falciparum strains

Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats

Context. The stem bark of the savanna tree Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases. Objective. This study seeks to investigate the possible antiallodynic and antihyperalgesic effects of the hydroethanolic stem bark extract of B. africana in a vincristine-induced peripheral neuropathy model in rats. Materials and Methods. 0.1 mg kg−1 vincristine was administered intraperitoneally for 5 days followed by 2 days break and continued for another 5 days to establish peripheral neuropathy in Sprague Dawley rats. Effects of Burkea africana extract (BAE) (50–1000 mg kg−1, p.o.) and pregabalin (10–100 mg kg−1, i.p.) were assessed on tactile, intermediate, mechanical, cold, and hot allodynia as well as in the Randall–Sellito test. Moreover, the levels of total proteins, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in sciatic nerve tissue homogenates were assayed. Results. BAE (50–1000 mg kg−1p.o.) showed significant antiallodynic and antihyperalgesic effects similar to pregabalin by increasing paw withdrawal latency and paw withdrawal threshold in all the behavioral tests used. Also, the extract decreased the levels of MDA (a lipid peroxidation product) as well as MPO and caused a significant increase in endogenous antioxidants (GSH) and antioxidant enzymes (SOD and CAT) in tissue homogenates of treated rats. Conclusions. Results from this study indicate that the hydroethanolic stem bark extract of B. africana exhibits antiallodynic and antihyperalgesic effects in vincristine-induced peripheral neuropathy in rats

Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450

Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential oils or their metabolites, like lavender oil and tea tree oil, have been reported to act as potential EDCs and contribute towards sex steroid imbalance in cases of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of essential oils with CYP17A1 and CYP19A1. Functional assays were performed using the radiolabeled substrates or Liquid Chromatography–High-Resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone, and (−)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these essential oils in various beauty and hygiene products is common, but only limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output and ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for novel compounds against hyperandrogenic disorders such as PCa and PCOS