Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications-A Review.

Quercetin is the major polyphenolic flavonoid that belongs to the class called flavanols. It is found in many foods, such as green tea, cranberry, apple, onions, asparagus, radish leaves, buckwheat, blueberry, broccoli, and coriander. It occurs in many different forms, but the most abundant quercetin derivatives are glycosides and ethers, namely, Quercetin 3-O-glycoside, Quercetin 3-sulfate, Quercetin 3-glucuronide, and Quercetin 3'-metylether. Quercetin has antioxidant, anti-inflammatory, cardioprotective, antiviral, and antibacterial effects. It is found to be beneficial against cardiovascular diseases, cancer, diabetes, neuro-degenerative diseases, allergy asthma, peptic ulcers, osteoporosis, arthritis, and eye disorders. In pre-clinical and clinical investigations, its impacts on various signaling pathways and molecular targets have demonstrated favorable benefits for the activities mentioned above, and some global clinical trials have been conducted to validate its therapeutic profile. It is also utilized as a nutraceutical due to its pharmacological properties. Although quercetin has several pharmacological benefits, its clinical use is restricted due to its poor water solubility, substantial first-pass metabolism, and consequent low bioavailability. To circumvent this limited bioavailability, a quercetin-based nanoformulation has been considered in recent times as it manifests increased quercetin uptake by the epithelial system and enhances the delivery of quercetin to the target site. This review mainly focuses on pharmacological action, clinical trials, patents, marketed products, and approaches to improving the bioavailability of quercetin with the use of a nanoformulation.

Therapeutic Potential of Nanocarrier-Mediated Delivery of Phytoconstituents for Wound Healing: Their Current Status and Future Perspective.

The treatment of wounds is a serious problem all over the world and imposes a huge financial burden on each and every nation. For a long time, researchers have explored wound dressing that speeds up wound healing. Traditional wound dressing does not respond effectively to the wound-healing process as expected. Therapeutic active derived from plant extracts and extracted bioactive components have been employed in various regions of the globe since ancient times for the purpose of illness, prevention, and therapy. About 200 years ago, most medical treatments were based on herbal remedies. Especially in the West, the usage of herbal treatments began to wane in the 1960s as a result of the rise of allopathic medicine. In recent years, however, there has been a resurgence of interest in and demand for herbal medicines for a number of reasons, including claims about their efficacy, shifting consumer preferences toward natural medicines, high costs and negative side effects of modern medicines, and advancements in herbal medicines brought about by scientific research and technological innovation. The exploration of medicinal plants and their typical uses could potentially result in advanced pharmaceuticals that exhibit reduced adverse effects. This review aims to present an overview of the utilization of nanocarriers in plant-based therapeutics, including its current status, recent advancements, challenges, and future prospects. The objective is to equip researchers with a comprehensive understanding of the historical background, current state, and potential future developments in this emerging field. In light of this, the advantages of nanocarriers based delivery of natural wound healing treatments have been discussed, with a focus on nanofibers, nanoparticles, nano-emulsion, and nanogels.

Ganoderma lucidum: Novel Insight into Hepatoprotective Potential with Mechanisms of Action.

Ganoderma lucidum (G. lucidum) has been widely used for its health benefits as an edible and traditional medicinal mushroom for thousands of years in Asian countries. It is currently used as a nutraceutical and functional food owing to its major bioactive compounds, polysaccharides and triterpenoids. G. lucidum exhibits a broad range of hepatoprotective impacts in various liver disorders, such as hepatic cancer, nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, hepatitis B, hepatic fibrosis, and liver injury induced by carbon tetrachloride (CCl4) and α-amanitin. G. lucidum protects the liver through a broad range of mechanisms that include the modulation of liver Phase I and II enzymes, the suppression of ß-glucuronidase, antifibrotic and antiviral actions, the regulation of the production of nitric oxide (NO), the maintenance of hepatocellular calcium homeostasis, immunomodulatory activity, and scavenging free radicals. G. lucidum could signify an encouraging approach for the management of various chronic hepatopathies, and its potential mechanisms make it a distinctive agent when used alone or with other drugs and applied as a functional food, nutraceutical supplement, or adjuvant to modern medicine. This review summarizes the hepatoprotective properties of G. lucidum with its various mechanisms of action on different liver ailments. Biologically active substances derived from G. lucidum are still being studied for their potential benefits in treating different liver ailments.

Antiprotozoal Activity of Thymoquinone (2-Isopropyl-5-methyl-1,4-benzoquinone) for the Treatment of Leishmania major-Induced Leishmaniasis: In Silico and In Vitro Studies.

Leishmaniasis, a neglected tropical parasitic disease (NTPD), is caused by various Leishmania species. It transmits through the bites of the sandfly. The parasite is evolving resistance to commonly prescribed antileishmanial drugs; thus, there is an urgent need to discover novel antileishmanial drugs to combat drug-resistant leishmaniasis. Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone; TQ), a primary pharmacologically active ingredient of Nigella sativa (black seed) essential oil, has been reported to possess significant antiparasitic activity. Therefore, the present study was designed to investigate the in vitro and in silico antileishmanial activity of TQ against various infectious stages of Leishmania major (L. major), i.e., promastigotes and amastigotes, and its cytotoxicity against mice macrophages. In silico molecular dockings of TQ were also performed with multiple selected target proteins of L. major, and the most preferred antileishmanial drug target protein was subjected to in silico molecular dynamics (MD) simulation. The in vitro antileishmanial activity of TQ revealed that the half-maximal effective concentration (EC50), half-maximal cytotoxic concentration (CC50), and selectivity index (SI) values for promastigotes are 2.62 ± 0.12 µM, 29.54 ± 0.07 µM, and 11.27, while for the amastigotes, they are 17.52 ± 0.15 µM, 29.54 ± 0.07 µM, and 1.69, respectively. The molecular docking studies revealed that squalene monooxygenase is the most preferred antileishmanial drug target protein for TQ, whereas triosephosphate isomerase is the least preferred. The MD simulation revealed that TQ remained stable in the binding pocket throughout the simulation. Additionally, the binding energy calculations using Molecular Mechanics Generalized-Born Surface Area (MMGBSA) indicated that TQ is a moderate binder. Thus, the current study shows that TQ is a promising antileishmanial drug candidate that could be used to treat existing drug-resistant leishmaniasis.

A Review on the Delivery of Plant-Based Antidiabetic Agents Using Nanocarriers: Current Status and Their Role in Combatting Hyperglycaemia.

Diabetes mellitus is a prevalent metabolic syndrome that is associated with high blood glucose levels. The number of diabetic patients is increasing every year and the total number of cases is expected to reach more than 600 million worldwide by 2045. Modern antidiabetic drugs alleviate hyperglycaemia and complications that are caused by high blood glucose levels. However, due to the side effects of these drugs, plant extracts and bioactive compounds with antidiabetic properties have been gaining attention as alternative treatments for diabetes. Natural products are biocompatible, cheaper and expected to cause fewer side effects than the current antidiabetic drugs. In this review, various nanocarrier systems are discussed, such as liposomes, niosomes, polymeric nanoparticles, nanoemulsions, solid lipid nanoparticles and metallic nanoparticles. These systems have been applied to overcome the limitations of the current drugs and simultaneously improve the efficacy of plant-based antidiabetic drugs. The main challenges in the formulation of plant-based nanocarriers are the loading capacity of the plant extracts and the stability of the carriers. A brief review of lipid nanocarriers and the amphipathic properties of phospholipids and liposomes that encapsulate hydrophilic, hydrophobic and amphiphilic drugs is also described. A special emphasis is placed on metallic nanoparticles, with their advantages and associated complications being reported to highlight their effectiveness for treating hyperglycaemia. The present review could be an interesting paper for researchers who are working in the field of using plant extract-loaded nanoparticles as antidiabetic therapies.

Suppression of Melanoma Growth in a Murine Tumour Model Using Orthosiphon stamineus Benth. Extract Loaded in Ethanolic Phospholipid Vesicles (Spherosome).

BACKGROUND: Orthosiphon stamineus Benth (O.S) is a traditional south-east Asian herb. The extract of O.S is used in the formulation of ethanolic nanolipid vesicle system to have considerable potential for tumour therapeutics. METHODS: The research objective is to develop and characterise the anticancer and antiangiogenic effect of O.S extract in the form of nano-ethanolic spherosomes (ESP) using phospholipids in melanoma. Spherosomes formulation of O.S was developed using the thin-film re-hydration method and converted to gel using Acrypol 1%. The formulations were subjected to optimisation and physical-chemical characterisations like particle size, surface charge, DSC, FTIR, and TEM. Cytotoxicity of O.S and ESP was studied using an endothelial cell line (EA. hy926). Furthermore, anti-melanoma effect of O.S spherosome gel was studied in albino mice after topical administration. RESULTS: ESP-6 with the ratio of extract (O.S): cholesterol: phospholipid (1: 6: 0.5) showed the highest entrapment efficiency (80.56 ± 0.84%) using ultraviolet spectroscopy. In-vivo permeation/penetration studies revealed deeper absorption of ESP-6 compared to a hydroethanolic gel of O.S. In-vitro and in vivo anti-melanoma studies demonstrated the significant tumour-suppressing effect of ESP-6 on murine melanoma. Percentage inhibition of tumour growth by O.S and ESP-6 at 3000 mg/kg showed to be 63.98 ± 7.86% and 87.76 ± 7.90%, respectively. CONCLUSION: Spherosome vesicles were developed with a smooth surface. The results demonstrated that O.S extract showed no toxicity when tested on the endothelial cell line. O.S loaded in spherosomes has the potential to lower the growth of melanoma in mice. The spherosomes loaded with O.S do not promote tumour growth or act as antiangiogenetic in melanoma.

Pharmacological basis for the antihypertensive activity of Grewia asiatica fruit extract.

In the management of cardiovascular disorders, medicines from herbal sources have played a vital role through centuries. The following study was commenced in order to lay possible pharmacological foundation associated with medicinal uses of edible fruit of Grewia asiatica in hypertension through in-vitro method. In this study isolated atrial preparation of Guinea pig was used where crude ethanolic extract of Grewia asiatica fruit (Ga.Cr) decreased the force and rate of spontaneous atrial contractions (0.03-10mg/kg). In isolated rat aortic ring preparations previously vasoconstricted by phenylephrine and High K+, it also resulted in dose dependent vasodilation (0.01-10 mg/kg).In the presence of L-NAME, the relaxation curve of Ga.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. The speculative analysis contemplated that Ga.Cr has blood pressure reducing potentials through inhibition of Ca++ influx via Ca++ channels, its release from intracellular stores and through other means like NO mediated pathways.

PEGylated Lipid Polymeric Nanoparticle-Encapsulated Acyclovir for In Vitro Controlled Release and Ex Vivo Gut Sac Permeation.

Currently, pharmaceutical research is directed wide range for developing new drugs for oral administration to target disease. Acyclovir formulation is having common issues of short half-life and poor permeability, causing messy treatment which results in patient incompliance. The present study formulates a lipid polymeric hybrid nanoparticles for antiviral acyclovir (ACV) agent with Phospholipon® 90G (lecithin), chitosan, and polyethylene glycol (PEG) to improve controlled release of the drugs. The study focused on the encapsulation of the ACV in lipid polymeric particle and their sustained delivery. The formulation developed for the self-assembly of chitosan and lecithin to form a shell encapsulating acyclovir, followed by PEGylation. Optimisation was performed via Box-Behnken Design (BBD), forming nanoparticles with size of 187.7 ± 3.75 nm, 83.81 ± 1.93% drug-entrapped efficiency (EE), and + 37.7 ± 1.16 mV zeta potential. Scanning electron microscopy and transmission electron microscopy images displayed spherical nanoparticles formation. Encapsulation of ACV and complexity with other physical parameters are confirmed through analysis using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. Nanoparticle produced was capable of achieving 24-h sustained release in vitro on gastric and intestinal environments. Ex vivo study proved the improvement of acyclovir's apparent permeability from 2 × 10-6 to 6.46 × 10-6 cm s-1. Acyclovir new formulation was achieved to be stable up to 60 days for controlled release of the drugs. Graphical abstract.

Histopathological effects on stomach, liver and kidney associated with Cedrus deodara root oil in ulcer induced rats (Wistar strain).

Cedrus deodara have been used traditionally in ayurvedic system against peptic ulcer. Present work is concerned with the determination of histopathological effects in ethanol induced ulcer on rats (Wistar Strain) treated with Cedrus deodara root oil at a dose of 200mg/kg and comparison of its antiulcer activity against control, positive control and standard anti-ulcer drug (Omeprazole). The aim was to find out the antiulcer effect of Cedrus deodara root oil and to observe histopathology of liver, kidney as well. 120 Albino rats were taken and divided into four groups i.e. A, B, C and D designated as control, positive control, standard and treated groups respectively. Normal and intact general architecture of mucosa and submucosa layers of stomach observed. No significant changes observed in thickness of epithelium, no inflammatory cells were present on the mucosa and submucosal layer and gastric glands were normal. Liver of albino rats, showed no dilation and congestion in central as well as portal vein. Kidney of albino rats exhibited no shrinkage in glomeruli, no congested and dilated renal corpuscles, neither hemolysis nor congested and dilated renal tubules were seen. It is concluded that C. deodara root oil has anti-ulcer properties without effecting kidney and liver tissues.

Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits.

BACKGROUND: Various extracts of Centella asiatica (Apiaceae) and its active constituent, asiaticoside, have been reported to possess wound healing property when assessed using various in vivo and in vitro models. In an attempt to develop a formulation with accelerated wound healing effect, the present study was performed to examine in vivo efficacy of asiaticoside-rich hydrogel formulation in rabbits. METHODS: Asiaticoside-rich fraction was prepared from C. asiatica aerial part and then incorporated into polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogel. The hydrogel was subjected to wound healing investigation using the in vivo incision model. RESULTS: The results obtained demonstrated that: i) the hydrogel formulation did not cause any signs of irritation on the rabbits' skin and; ii) enhanced wound healing 15% faster than the commercial cream and > 40% faster than the untreated wounds. The skin healing process was seen in all wounds marked by formation of a thick epithelial layer, keratin, and moderate formation of granulation tissues, fibroblasts and collagen with no fibrinoid necrosis detected. CONCLUSION: The asiaticoside-rich hydrogel developed using the freeze-thaw method was effective in accelerating wound healing in rabbits.

Antiangiogenic activity of sophorolipids extracted from refined bleached deodorized palm olein.

OBJECTIVES: Sophorolipids (SLs) are a group of surface-active glycolipids produced by a type of nonpathogenic yeast Candida bombicola in the presence of vegetable oil through fermentation technology. SLs have shown antitumor activity; however, the mechanism of action underlying the anticancer activity of SLs is poorly understood. This work evaluated the anticancer activity of SLs fermented from palm oil by exploring its antiangiogenic activity. MATERIALS AND METHODS: The SLs that were fermented and further characterized for their biochemical activities. Cytotoxicity study was performed to assess cytostatic properties. A series of in vitro and ex vivo angiogenesis assay was also carried out. The relative fold change in the expression of p53 mRNA by SLs was also studied. RESULTS: Altogether, the data show that SLs derived from palm oil fermentation process inhibited neovascularization in the ex vivo tissue segments and also the endothelial cell proliferation between 50% and 65% inhibition as a whole. The palm oil derived SLs also caused downregulation of the suppression level of vascular endothelial growth factor and also upregulate the p53 mRNA level. The analytical studies revealed the presence of high amount of phenolic compounds but with relatively weak antioxidant activity. The gas chromatography-mass spectrometry studies revealed abundant amount of palmitic and oleic acid, the latter an established antiangiogenic agent, and the former being proangiogenic. CONCLUSION: Therefore, it can be concluded from this study that SLs derived from fermented palm oil have potent antiangiogenic activity which may be attributed by its oleic acid component.

Hypermucoviscous Klebsiella syndrome it's in the community!

Hypermucoviscous Klebsiella syndrome is a unique syndrome caused by a new variant of Klebsiella pneumoniae (KP), characterized by abscess formation at distant body sites. This emerging KP strain is different from the usual classic strains in having the rmp gene which increases capsule formation making this strain resistant to phagocytosis and helping in its dissemination to distant organs. A 50 years old diabetic man presented with facial swelling after dental procedure which progressively increased despite being on antibiotics. On examination he was febrile, had neck swelling with signs of inflammation and tender hepatomegaly. Ultrasonography showed submental and liver abscesses which were subsequently drained and both cultures isolated KP with hypermucoid colonies on agar plate and a positive string test indicating the presence of this new hypervirulent strain of KP. Therefore, a diagnosis of Hypermucoviscous Klebsiella syndrome should be considered in all patients who present with KP infection with multiple organ abscesses..

Assessment of Cedrus deodara root oil on the histopathological changes in the gastrointestinal tissues in rats.

The present study was designed to investigate the effect of Cedrus deodara root oil on the histopathology of different gastrointestinal organs of Wistar rats. This oil was used traditionally as an anti-ulcer agent in the Indus Unic System and extracted from the plant root by destructive distillation method. A total of 90 rats were taken and divided into groups A, B and C, each comprising of 30 animals. The animals of group B and C were given 0.5 ml/kg and 2.5 ml/kg of C. deodara oil respectively while group A served as control and administered vehicle only. The treatment was given to the animals ones only for 24 hours. All animals were sacrificed and the organs like esophagus, stomach and ileum were taken out. Tissue processing and staining procedure was then carried out for any pathological changes in the animal tissues during microscopic examination. The results indicated that Cedurs deodara root oil at both doses 0.5ml/ kg and 2.5 ml/kg exhibited some adverse effects such as erosion of epithelium, edema on sub-mucosal and mucosal layers, congestion of blood vessels as well as presence of inflammatory cells on esophagus, stomach and ileum were seen. Moreover shortening of villi was also seen at both doses. A study conducted on mammalian toxicity previously on rats revealed that the C. deodara root oil used is not very toxic and comes under least toxic group as standardized by toxicologists. Based on the results obtained it was concluded that C. deodara root oil produced some adverse changes in the tissues of GIT when given at 0.5 ml/kg and 2.5 ml/kg doses but the effects were not lethal therapeutically at this dose LC50 16.5 ml/kg. The plant oil showed some toxicity and needs further detailed studies to assess its potential toxicity and therapeutic status before using this material as drug.