Clerodendrum Glandulosum Lindl.: A Review of Ethnopharmacology, Pharmacological Potentials, and their Mechanism of Action.

Clerodendrum glandulosum Lindl. is popularly known for its traditional herbal remedies and therapeutic properties among the people of Northeast Indian communities, as well as Chinese traditional medicine. For the myriad pharmacological properties, viz., anti-hypertensive, hypolipidemic, hepatoprotective, anti-inflammatory, and neuroprotective, planting this species in kitchen gardens is a common practice to treat various ailments, especially hypertension, diabetes, and other metabolic complications. Different phytochemicals, representing the diverse classes of secondary metabolites comprising physiological and phytopharmaceutical significance, have been reported from C. glandulosum. Compounds with terpenoids, steroids, and phenolics are in demand in the pharmaceutical industry. An overview of the mechanism of action of the prominent compounds has also been collated for future research on C. glandulosum-based therapeutics. Current information focuses on this important medicinal plant's ethnomedicinal use, phytochemistry, pharmacology, associated mechanisms, and toxicology. This review will help explore this potential medicinal plant, which can pave the path for its application in the pharmaceutical industry.

Nutritional Composition and Pharmacological Activity of Musa balbisiana Colla Seed: An Insight into Phytochemical and Cellular Bioenergetic Profiling.

Musa balbisiana Colla belongs to the family Musaceae which is well-known for its nutritional and pharmacological properties. Here, we have analysed the phytochemical content and evaluated the nutritional, antioxidant, anti-glycation, α-amylase, and α-glucosidase inhibition potential. Moreover, for the first time, we have studied the bioenergetic profiles of the bioactive fractions of M. balbisiana seeds extract against oxidative stress-related mitochondrial and cellular dysfunction using XFe24 extracellular flux analyzer. M. balbisiana seeds have high nutritional values with significant levels of carbohydrates, starch, protein, and minerals (Ca, Na, Mg, Cu, Fe, and Zn). Bioactivity-guided fractionation of the methanolic extract of M. balbisiana seeds revealed that the ethyl acetate fraction (EAF) showed the highest antioxidant, anti-glycation, and phytochemical content as compared to other fractions. Moreover, the EAF showed a lower α-amylase inhibition and a higher α-glucosidase inhibitory activity. Most importantly, our GC-MS analyses of EAF revealed the presence of unique and previously unreported 14 phytochemical compounds. A strong correlation between the biological activities and total phenolic/tannin content was observed. In addition, the bioactive fraction of M. balbisiana seeds (EAF) improved the bioenergetic profiles of free fatty acid-induced oxidative stress with a concomitant increase in ATP production, and respiratory and glycolytic capacity. Altogether, our findings suggest that M. balbisiana seeds can be used as a natural supplement to boost antioxidant levels and combat oxidative stress and non-enzymatic glycation.

Ultrasound-Assisted Extraction of Verbascoside from Clerodendrum glandulosum Leaves for Analysis of Antioxidant and Antidiabetic Activities.

Verbascoside (VER) is a phenylethanoid glycoside compound found in Clerodendrum species and is an important part of traditional medicine. It is found in the leaves of Clerodendrum glandulosum, which is taken as a soup or vegetable and also utilized in traditional medicine by the people of Northeast India, especially against hypertension and diabetes. In the present study, VER was extracted from C. glandulosum leaves using ultrasound-assisted extraction through the solvent extraction method (ethanol-water, ethanol, and water). The ethanol extract had the highest phenolic and flavonoid contents, viz., 110.55 mg GAE/g and 87.60 mg QE/g, respectively. HPLC and LC-MS were used to identify the active phenolic compound, and VER was found to be the main component present in the extraction with a molecular weight of 624.59 g/mol. NMR (1H, 2D-COSY) analysis showed the presence of hydroxytyrosol, caffeic acid, glucose, and rhamnose in the VER backbone. Further, different antioxidant activities and antidiabetic and antihyperlipidemia enzyme markers' inhibition against VER-enriched ethanol extract were evaluated. The results showed that ultrasound extraction of polyphenols using ethanol from C. glandulosum could be a promising technique for the extraction of bioactive compounds.

Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.

A pharmacological perspective of banana: implications relating to therapeutic benefits and molecular docking.

Banana is one of the most nutritious fruits, as it is rich in carbohydrates, proteins, fatty acids, and minerals. Banana has been used in traditional medicines for managing coughs and colds, ulcers, burns, and diarrhea. Banana contains various bioactive compounds, such as alkaloids, phenols, flavonoids, tannins, and saponins, with reported therapeutic benefits, including antioxidant, anti-diabetic, anti-cancer, anti-inflammatory, and anti-microbial activities. The present review focuses on a comprehensive overview of the nutritional and biological properties and phytochemicals of different species of banana and its different parts. Although detailed characterization of the compounds that are present in many parts of the plant has been carried out, chemical profiling of the seed, pseudostem, and leaves of banana is lacking and requires further exploration. Moreover, the functions of the reported compounds were elucidated using computational tools, supporting their potential role in managing life-threatening diseases and physiological complications.

A Comprehensive Review of Garcinia pedunculata Roxb. and its Therapeutic Potential.

Garcinia pedunculata Roxb.(GP) belongs to the family of Clusiaceae and is an evergreen tree that grows in semi-wild conditions and is widely distributed throughout the Northeastern part of India. Traditionally, this plant is believed to be of immense medicinal importance and is used for the treatment of various ailments. In Assam, the acidic fruit of GP is effectively used in folklore medicine to treat gastrointestinal disorders and is an integral part of ethnic Assamese cuisine. The ripe fruit, seldom consumed fresh or raw, is cut into thin slices, sun-dried for preservation as it is believed that the medicinal property of the fruit increases as it ages. With much traditional claims and beliefs regarding the medicinal properties of this plant, many therapeutic potentials of GP have been explored through research till now, including its antioxidant, antibacterial, antifungal, anthelmintic, hypolipidemic, antidiabetic, hepatoprotective, neuroprotective, and nephroprotective properties. Moreover, the presence of polyphenols, flavonoids along with bioactive components like hydroxycitric acid, garcinol, and cambogin have also been reported from this plant, thereby increasing its research avenues. Even with the available knowledge, there is a huge lacking in the understanding of its underlying molecular mechanism responsible for the therapeutic properties, pharmacological mode of action, and its effect in different pathological conditions, along with detailed information about its chemical composition. This review mainly aims to summarise the potentially beneficial properties of GP that have already been reported, along with identifying the new avenues that still need to be addressed, thereby increasing the future prospect for in-depth research on this plant, along with its distribution and conservation status.

Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability.

Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil's physiochemical and microbial parameters of its cultivation sites.

Assessment of nutritional value and quantitative analysis of bioactive phytochemicals through targeted LC-MS/MS method in selected scented and pigmented rice varietals.

Scented (joha) and black rice indigenous to northeast region (NER) of India are the two among 40,000 varieties of species Oryza sativa, prevalent for its great aroma, medicinal property, and/or equally noteworthy taste. Biochemical and target-based liquid chromatography mass spectrometry (LCMS) analysis was performed to identify and quantify the different phytonutrients from the selected rice grains of those two varieties. Biochemical assay revealed that the selected black rice (Chakhao Amubi) contains ∼1.8-fold higher amount of total phenolic and ∼2.3-fold higher amount of total flavonoid than the scented rice grain (Kon joha). The total starch content was significantly lower in scented rice in comparison to black rice grain. The health beneficial ratio of ω-6/ω-3 essential unsaturated fatty acid is notably better in scented rice grain than black rice grain. The targeted LC-MS/MS analysis confirms the presence of oryzanol and ferulic acid in both the samples. The presence of 4-hydroxy benzoic acid, apigenin, tricin, avenasterol, coumarin, coumaric acid, phenyl alanine, caffeic acid, and α-tocophenol were confirmed in the scented rice, whereas the black rice confirms the presence of protocatechuic acid and dehydroxy myricetin. Further the quantitative analysis showed that the lipids lysophosphatidylinositol (LPI) 16:0, lysophosphatidyl ethanolamine (LPE) 14:0, lysophosphatidyl choline (LPC) 18:2, LPE 18:2, phosphatidyl etanolamine (PE), along with oryzanol, hydroxy docosanoic acid are at least threefold higher in scented rice varietal; whereas, in Chakhao Amubi, the content of petunidin galactoside, LMMPE18:2, PC14:0 are higher than the scented rice grain. In conclusion, different phytonutrients including phenol, polyphenol, and flavonoid have been identified as bioactive phytochemicals in selected rice varietals. PRACTICAL APPLICATION: This work will provide the information about the nutritional benefit of studied rice varietals. The used targeted LC-MS/MS analysis will provide the one-step information about the bioactive phytochemicals. Overall, this study will help to commercialize those varieties with proper scientific evidences.

Phytochemical screening, antioxidant, antityrosinase, and antigenotoxic potential of Amaranthus viridis extract.

OBJECTIVE: Amaranthus viridis (Amaranthaceae) widely distributed all over the world, growing under a wide range of climatic conditions and has been utilized as a medicinal herb in traditional Ayurvedic medicine as antipyretic agents, also for the treatment of inflammation, ulcer, diabetic, asthma and hyperlipidemia. The aim of the study was designed to evaluate the chemical composition and antioxidant and biological properties of different fractions obtained from A. viridis. MATERIALS AND METHODS: Four different extracts of A. viridis were prepared using aqueous, methanol, chloroform, and hexane and investigated their antioxidant potential using free radical scavenging activities such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and nitric oxide (NO) radical scavenging activity, as well as metal chelating activity. In addition, antityrosinase and antigenotoxicity properties were also evaluated by the standard in vitro methods. Finally, the active methanolic extract (ME) was investigated for identifying the phenolic compounds using UPLC-MS/MS. RESULTS: In the present study, chlorogenic acid, gulonic acid, and kaempferol were found to be the major components responsible for the antioxidant activity of A. viridis extract as evidenced from UPLC-MS/MS. Furthermore, the ME of A. viridis revealed excellent antioxidant activities such as DPPH radical scavenging activity (IC50= 47.23 ± 0.66 µg/mL), NO radical scavenging activity (IC50= 64.33 ± 2.01 µg/mL), hydrogen peroxide (H2O2) radical scavenging activity (IC50= 33.21 ± 3.3 µg/mL), ABTS radical scavenging activity (IC50= 47.61 ± 1.31 µg/mL), metal chelating activity (IC50= 32.1 ± 1.11 µg/mL), as well as lipid peroxidation inhibiting activity (IC50= 112 ± 1.21 µg/mL). Furthermore, ME revealed that the protective effects of extract were observed on H2O2-induced DNA damages with alkaline comet assay. CONCLUSIONS: Taken together, the study concluded that the promising antioxidant capacities of A. viridis extract can further be utilized in various agricultural, pharmaceutical, and food applications.

Anticoagulant mechanism, pharmacological activity, and assessment of preclinical safety of a novel fibrin(ogen)olytic serine protease from leaves of Leucas indica.

The harnessing of medicinal plants containing a plethora of bioactive molecules may lead to the discovery of novel, potent and safe therapeutic agents to treat thrombosis-associated cardiovascular diseases. A 35 kDa (m/z 34747.5230) serine protease (lunathrombase) showing fibrin(ogen)olytic activity and devoid of N- and O- linked oligosaccharides was purified from an extract of aqueous leaves from L. indica. The LC-MS/MS analysis, de novo sequencing, secondary structure, and amino acid composition determination suggested the enzyme's novel characteristic. Lunathrombase is an αß-fibrinogenase, demonstrating anticoagulant activity with its dual inhibition of thrombin and FXa by a non-enzymatic mechanism. Spectrofluorometric and isothermal calorimetric analyses revealed the binding of lunathrombase to fibrinogen, thrombin, and/or FXa with the generation of endothermic heat. It inhibited collagen/ADP/arachidonic acid-induced mammalian platelet aggregation, and demonstrated antiplatelet activity via COX-1 inhibition and the upregulation of the cAMP level. Lunathrombase showed in vitro thrombolytic activity and was not inhibited by endogenous protease inhibitors α2 macroglobulin and antiplasmin. Lunathrombase was non-cytotoxic to mammalian cells, non-hemolytic, and demonstrated dose-dependent (0.125-0.5 mg/kg) in vivo anticoagulant and plasma defibrinogenation activities in a rodent model. Lunathrombase (10 mg/kg) did not show toxicity or adverse pharmacological effects in treated animals.

Phytochemical portfolio and anticancer activity of Murraya koenigii and its primary active component, mahanine.

Murraya koenigii, a plant belonging to the Rutaceae family is widely distributed in Eastern-Asia and its medicinal properties are well documented in Ayurveda, the traditional Indian system of medicine. Through systematic research and pharmacological evaluation of different parts of the plant extracts has been shown to possess antiviral, anti-inflammatory, antioxidant, antidiabetic, antidiarrhoeal, antileishmanial, and antitumor activity. In the plant extracts, carbazole alkaloid, mahanine has been identified as the principle bioactive component among several other chemical constituents. Scientific evidence derived not only from in vitro cellular experiments but also from in vivo studies in various cancer models is accumulating for the pronounced anticancer effects of mahanine. The primary objective of this review is to summarize research data on cytotoxic chemical constituents present in different parts of Murraya koenigii and the anticancer activity of mahanine along with the recent understanding on the mechanism of its action in diverse cancer models. The information on its bioavailability and the toxicity generated from the recent studies have also been incorporated in the review.

In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract.

The study aimed to identify the phenolic compounds present in Centella asiatica (L.) (C. asiatica) extract and evaluate the respective antioxidant potential as well as its cholesterol-lowering effects in the experimental animal model. Herein, the antioxidant potential of extracts was assessed by its free radical scavenging activity such as 2, 2-diphenyl -1- picrylhydrazyl as well as reducing capability. The anti-hyperlipidemic effects of C. asiatica extract (CAE) were evaluated in high cholesterol-fed (HCF) rats for 4 weeks, where different concentrations of extracts (0.25, 0.5, and 1 g/kg/day) were orally administrated daily. Lipid and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD), together with the indices of hepatic functions were also examined. C. asiatica revealed excellent free radical scavenging activity as revealed by 2-2- diphenyl-1-picryl-hydrazyl (DPPH) assay, with the IC50 values (9.62 ± 0.88 µg/mL). Furthermore, C. asiatica extracts and fenofibrate remarkably lowered the level of TC, TG, LDL-C, and showed elevated levels of HDL-C, SOD. The histopathological observations further demonstrated clear differentiation and structural changes in liver of HCF and CAE treated group. Furthermore, gulonic acid, ferulic acid, kaempferol, chlorogenic acid, and asiatic acid were identified to be the major components which might be responsible for the antioxidant activity of the C. asiatica extract as evidenced from an ultra-high performance liquid chromatography-mass spectrometer. Taken together, these results signifies the excellent antioxidant and anti-hyperlipidemic properties of C. asiatica leaf extracts, which might be useful for the treatment of oxidative-stress related diseases such as hyperlipidemia.

Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress.

The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer, and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark (ZJRB) against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF), and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD, and CAT) and cytokine levels (TNF-α, Il-1ß, and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of ZJRB as good therapeutic agent for liver toxicity and chronic inflammation.

Rapid screening and identification of phenolic antioxidants in Hydrocotyle sibthorpioides Lam. by UPLC-ESI-MS/MS.

The aim of the study was to identify the phenolic compounds present in Hydrocotyle sibthorpioides (HS), Centella asiatica (CA) and Amaranthus viridis (AV) extracts and investigate their respective antioxidant activities. Herein, an ultra-high pressure liquid chromatography-mass spectrometer (UPLC-MS/MS) analytical method has been developed for the separation, and systematic characterization of the phenolic compounds in HS, CA and AV extracts and was compared along with ten standard phenolic compounds. Additionally, in vitro antioxidant activity of the phenolic compounds was also determined. The HS extract revealed excellent antioxidant activity such as 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (IC50=19.7 ± 1.2 µg/mL), total reduction capability (0.169 ± 0.003 at 100 µg/mL), nitric oxide radical scavenging activity (IC50=39.33 ± 3.2 µg/mL), metal chelating activity (IC50=56.51 ± 3.6 µg/mL) and inhibition of lipid peroxidation (IC50=12.34 ± 2.3 µg/mL) as compared to CA and AV extracts. Furthermore, catechin, epicatechin, quercetin and chlorogenic acid were found to be the major components responsible for the antioxidant activity of the HS extract as evidenced from UPLC-MS/MS. Taken together, this study demonstrates the promising antioxidant properties of the HS extract, which can further be utilized in various pharmaceutical, food, and agricultural applications.

Hypolipidemic effect of different extracts of Clerodendron colebrookianum Walp in normal and high-fat diet fed rats.

Clerodendron colebrookianum Walp (family, Verbenaceae) has been used as a home remedy by the Mizo people of north eastern (NE) region of India in their folklore medicine as a cardioprotective (mainly against high blood pressure) agent. The scientific basis for their use has yet to be established. Therefore, in this investigation an attempt has been made to study the effect of different extracts of the leaves of Clerodendron colebrookianum Walp (CC) on serum lipid profile which is closely associated with many cardiovascular diseases. It was found that after administration of both crude and organic extracts the serum lipid profile, i.e. total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) lowered significantly (P<0.001) from their respective control except TG in methanol extract (ME)-treated rats. The decreased percentage of TC, TG and LDL after administration of crude extract (CE) and ethylacetate extract (EE) with normal diet were found to be 35, 39 and 48%, and 33, 18 and 91%, respectively, after 7 days of treatment. In case of ME the lowering of TC and LDL were noted to be 41 and 85%, respectively. Both TC and TG were lowered significantly (P<0.001) even after the administration of crude extract against high-fat diet. Significant increase of cardioprotective lipid, i.e high density lipoprotein (HDL) after administration of EE (46%) and ME (38%) was another interesting finding of this experiment. Total cholesterol:HDL and LDL:HDL ratios were significantly lower in the experimental group. Therefore, it was concluded that the leaves of CC have definite cardioprotective potentiality, and there is a valid scientific basis for consuming it for better health in NE region of India.