Plant-derived Drugs Research Articles

Liquid Chromatography-Mass Spectrometry Characterized Hydrolysate Fractions Possess Anticancer Activity In Vitro

To find new plant-derived antitumor drugs, hydrolysate and fractions of poplar were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for their inhibitory effect against liver cancer HepG-2 cells. Strong cytotoxicity of hydrolysate was revealed at processing temperature of 180 °C or above. The hydrolysate formed at 180 °C was sequentially extracted using organic solvent to obtain five fractions, and only the diethyl ether-soluble fraction (FDe) showed specific cytotoxicity. The eluted fraction of acetone/n-hexane (F1) was further isolated by column chromatography separation from the FDe fraction at a yield of 70%, and could severely decrease cell viability. LC-MS chromatography indicated that 5-hydroxymethyl furfural, ρ-hydroxybenzoic acid and syringaldehyde were the main compounds in the F1 fraction. Furthermore, the results of flow cytometry, Western blotting, and polymerase chain reaction indicated that syringaldehyde could tightly control the growth and metabolism of HepG-2 cells. The findings could move forward the value-added applications of lignocellulosic hydrolysate on traditional medicines.

Promising Strategies in Plant-Derived Treatments of Psoriasis-Update of In Vitro, In Vivo, and Clinical Trials Studies.

Psoriasis is a common, chronic systemic inflammatory disease affecting 125 million people worldwide. It is associated with several important conditions, including psoriatic arthritis, cardiometabolic syndrome, and depression, leading to a significant reduction in patients’ quality of life. Current treatments only reduce symptoms, not cure. This review discusses the mechanisms involved in the initiation and development of the disease, the role of oxidative stress in this autoimmune disease, as well as potential therapeutic options with substances of natural origin. The main aim of the study is intended to offer a review of the literature to present plants and phytochemicals that can represent potential remedies in the fight against psoriasis. We identified many in vitro, in vivo, and clinical trials studies that evaluated the relationship between chosen natural substances and immune system response in the course of psoriasis. We sought to find articles about the efficacy of potential natural-derived drugs in controlling symptoms and their ability to maintain long-term disease inactivity without side effects, and the result of our work is a review, which highlights the effectiveness of plant-derived drugs in controlling the inflammatory burden on psoriatic patients by decreasing the oxidative stress conditions.

CLOVE/QURANFUL (Syzygium aromaticum L.): A REVIEW ON ITS POTENTIAL BENEFITS IN UNANI MEDICINE, BIOACTIVITIES AND CURRENT SCIENTIFIC APPLICATIONS

Background: Herbal drugs have been shown to be a valuable source of new pharmaceutical molecules that have been utilised to treat serious disorders. Clove (Syzygium aromaticumL.) is a plant-derived drug with a long history of usage in Unani medicine due to its numerous pharmacological benefits attributable to its phytoconstituents. Aims and objectives: The basic aim of this article is to present a comprehensive report on the potential benefits of clove as described in the Unani system of medicine as well as present an analysis of contemporary scientific researches in order to explore the prospects for its application. Materials and methods:Classical data were collected from the manuscripts of Unani medicine like Al Qanoon Fit Tib, Khazain al-Advia, Makhzan al-Advia, Muheet-i-Azam, Al-Jami li Mufradat al- Advia wa'l Aghziya, etc. An online search was performed in Pub Med, Scopus, Wiley Online Library and Google Scholar to elucidate the various pharmacological activities of clove. Results: The potential of clove shown by its chemical composition, therapeutic use and bioactivities revealed its antibacterial, anti-fungal, anti-viral, anti-oxidant, anti-inflammatory, anticancer, hepatoprotective and nephroprotective effects. Sesquiterpenes, monoterpenes, hydrocarbon, and phenolic compounds, are found in abundance in S. aromaticu, with eugenyl acetate, eugenol, and β-caryophyllene being the mostimportant phytochemicals reportedin clove oil. Several in vitro and in vivo studies have demonstrated its multiple bioactivities, exhibiting its effect on diseases including halitosis, odontalgia, thyroidcancer, rheumatoidarthritis, nephrotoxicity, and vaginal candidiasis, among others. Conclusion: The several studies evaluated in this article support clove's traditional use in Unani medicine, indicating its usefulness for a variety of ailments. Future research should focus on developing new clove derivative-based formulations

Antibacterial Activity and Stability of Methanol Extract from Thamnolia subuliformis in Vitro

The objective of the study was preliminarily explore the antibacterial activity and stability of Thamnolia subuliformis in vitro, the plate drilling method was used to determine the antibacterial activity of methanol extract of Thamnolia subuliformis against common pathogenic bacteria in vitro. The indicator bacteria of Staphylococcus aureus was used to determine the effects of factors such as different temperature, pH and UV irradiation time on antibacterial stability. Petroleum ether, ethyl acetate and n-butanol were used to extract the methanol extract, determine the polarity of its antibacterial active substances, and determine the content of usnic acid. The results showed that the methanol extract of Thamnolia subuliformis had good antibacterial effect on Gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, Listeria stephensi, Staphylococcus surface, Listeria evansi, paratyphoid A, paratyphoid B of Gram-negative bacteria and Candida albicans. The minimum inhibitory concentration and minimum bactericidal concentration against Staphylococcus aureus were 0.625 and 10 mg/mL respectively; The results of antibacterial stability test showed that temperature had no significant effect on the antibacterial activity of methanol extract of Thamnolia subuliformis（P>0.05）, and it still had high antibacterial activity after treatment at 100 ℃ for 30 min; The antibacterial activity of UV irradiation for 40 min and 50 min decreased significantly (P 0.05）, showing high antibacterial activity. When the pH was high (8.0, 10.0) or low (2.0, 4.0), the antibacterial activity of the treatment group decreased significantly (P<0.05), and decreased with the increase or decrease of pH, The content of usnic acid in methanol extract and ethyl acetate extract of Thamnolia subuliformis was 0.8613% and 0.9379%, respectively. The results show that the methanol extract of Thamnolia subuliformis has a certain broad-spectrum antibacterial effect, low concentration and good stability. It can be used for the development and utilization of natural food preservatives and plant-derived antibacterial drugs.

Comparative Anatomical and Biochemical Characterization of Three Morphotypes of Ancient Medicinal Plant Cissus quadrangularis L.

The emphasis on search of new plant-derived drugs containing medicinally useful chemical constituents has increased in the last two decade. Additionally medicinal herbs are considered to be a chemical factory as it contains multitude of chemical compounds like alkaloids, glycosides, saponins, resins, oleoresin, and oils (essential and fixed). The studies on medicinal plant begin with knowing the anatomy and morphology of the plant followed by biochemical charcetrization and extraction of compounds of interest.Cissus quadrangularis L. is an important medicinal plant with diverse applications in alternative medicines. The extracts obtained from plant were used in treatment from ancient time as documented in Ayurveda.

Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids.

Cancer is a complex multifactorial disease that results from alterations in many physiological and biochemical functions. Over the last few decades, it has become clear that cancer cells can acquire multidrug resistance to conventional anticancer drugs, resulting in tumor relapse. Thus, there is a continuous need to discover new and effective anticancer drugs. Natural products from plants have served as a primary source of cancer drugs and continue to provide new plant-derived anticancer drugs. The present review describes plant-based alkaloids, which have been reported as active or potentially active in cancer treatment within the past 4 years (2017–2020), both in preclinical research and/or in clinical trials. In addition, recent insights into the possible molecular mechanism of action of alkaloid prodrugs naturally present in plants are also highlighted.

Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity.

Dengue is a serious public health concern worldwide, with ∼3 billion people at risk of contracting dengue virus (DENV) infections, with some suffering severe consequences of disease and leading to death. Currently, there is no broad use vaccine or drug available for the prevention or treatment of dengue, which leaves only anti-mosquito strategies to combat the dengue menace. The present study is an extension of our earlier study aimed at determining the in vitro and in vivo protective effects of a plant-derived phytopharmaceutical drug for the treatment of dengue. In our previous report, we had identified a methanolic extract of aerial parts of Cissampelos pareira to exhibit in vitro and in vivo anti-dengue activity against all the four DENV serotypes. The dried aerial parts of C. pareira supplied by local vendors were often found to be mixed with aerial parts of another plant of the same Menispermaceae family, Cocculus hirsutus, which shares common homology with C. pareira. In the current study, we have found C. hirsutus to have more potent anti-dengue activity as compared with C. pareira. The stem part of C. hirsutus was found to be more potent (∼25 times) than the aerial part (stem and leaf) irrespective of the extraction solvent used, viz., denatured spirit, hydro-alcohol (50:50), and aqueous. Moreover, the anti-dengue activity of stem extract in all the solvents was comparable. Hence, an aqueous extract of the stem of C. hirsutus (AQCH) was selected due to greater regulatory compliance. Five chemical markers, viz., Sinococuline, 20-Hydroxyecdysone, Makisterone-A, Magnoflorine, and Coniferyl alcohol, were identified in fingerprinting analysis. In a test of primary dengue infection in the AG129 mice model, AQCH extract at 25 mg/kg body weight exhibited protection when administered four and three times a day. The AQCH was also protective in the secondary DENV-infected AG129 mice model at 25 mg/kg/dose when administered four and three times a day. Additionally, the AQCH extract reduced serum viremia and small intestinal pathologies, viz., viral load, pro-inflammatory cytokines, and vascular leakage. Based on these findings, we have undertaken the potential preclinical development of C. hirsutus-based phytopharmaceutical, which could be studied further for its clinical development for treating dengue.

A Review of Medicinal Plants with Antiviral Activity Available in Bangladesh and Mechanistic Insight Into Their Bioactive Metabolites on SARS-CoV-2, HIV and HBV.

Currently, viral infection is the most serious health issue which causing unexpected higher rate of death globally. Many viruses are not yet curable, such as corona virus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), hepatitis virus, human papilloma virus and so others. Furthermore, the toxicities and ineffective responses to resistant strains of synthetic antiviral drugs have reinforced the search of effective and alternative treatment options, such as plant-derived antiviral drug molecules. Therefore, in the present review, an attempt has been taken to summarize the medicinal plants reported for exhibiting antiviral activities available in Bangladesh along with discussing the mechanistic insights into their bioactive components against three most hazardous viruses, namely SARS-CoV-2, HIV, and HBV. The review covers 46 medicinal plants with antiviral activity from 25 families. Among the reported 79 bioactive compounds having antiviral activities isolated from these plants, about 37 of them have been reported for significant activities against varieties of viruses. Hesperidin, apigenin, luteolin, seselin, 6-gingerol, humulene epoxide, quercetin, kaempferol, curcumin, and epigallocatechin-3-gallate (EGCG) have been reported to inhibit multiple molecular targets of SARS-CoV-2 viral replication in a number of in silico investigations. Besides, numerous in silico, in vitro, and in vivo bioassays have been demonstrated that EGCG, anolignan-A, and B, ajoene, curcumin, and oleanolic acid exhibit anti-HIV activity while piperine, ursolic acid, oleanolic acid, (+)-cycloolivil-4′-O-β-d-glucopyranoside, quercetin, EGCG, kaempferol, aloin, apigenin, rosmarinic acid, andrographolide, and hesperidin possess anti-HBV activity. Thus, the antiviral medicinal plants and the isolated bioactive compounds may be considered for further advanced investigations with the aim of the development of effective and affordable antiviral drugs.

Terminalia chebula reduces melanoma cell proliferation and increases apoptosis by inhibiting tyrosinase

Recently, research on using plant-derived drugs as anticancer agents has been greatly developed. Terminalia chebula (T. chebula) Retz., the mature fruit of T. chebula, contains active ingredients that have antioxidant, antimicrobial, and antitumor effects. Because traditional Chinese medicine components have unstable physical and chemical properties, such as poor solubility, fast decomposition, and high irritation, drug nanocarriers that effectively increase their solubility and reduce irritation are desirable. Additionally, T. chebula fruit can inhibit tyrosinase activity. This study aimed to determine whether T. chebula nanostructured lipid carriers can regulate the proliferation and apoptosis of melanoma cells by inhibiting tyrosinase activity. Tyrosinase activity in drug-treated melanoma cells was detected by MTT and DOPA oxidation assays, and cell proliferation rate was observed. Western blot (MTT) was used to detect the activity of apoptotic factors, and flow cytometry was used to determine the apoptotic rate. The results showed that tyrosinase activity and cell proliferation rate decreased with increasing drug concentration in cultured cells. Furthermore, the inhibitory effect was concentration-dependent. Additionally, cells cultured with a high concentration of T. chebula nanostructured lipid carriers could activate apoptotic factors and increase cell apoptosis. Thus, this study showed that T. chebula fruit nanostructured lipid carriers could inhibit the proliferation of melanoma cells and increase apoptosis by inhibiting tyrosinase activity, demonstrating a new plant-derived drug for melanoma treatment.

Molecular quantification, a new strategy for quality control of Chinese patent medicine containing animal-derived crude drug: Qi She in Jinlong capsule as an example

Quality control for Chinese patent medicine (CPM) containing animal-derived crude drug(s) is rather difficult. The methods based on chemical composition analysis, which are commonly used in CPM consisted of plant-derived crude drugs, are often not applicable for CPM containing animal-derived crude drug, because the effective constituents of most animal-derived crude drugs remain unknown. Even if there are such methods, they are usually qualitative rather than quantitative, and the specificity is generally poor. Here we proposed a molecular quantification method for CPM containing animal-derived crude drug, based upon the hypothesis that the amount of remnant DNA fragments could reflect feeding quantity of the crude drugs and thus ensure the quality of the CPM. Take Jinlong capsule [a hepatocellular carcinoma-resisting Chinese patent medicine comprising of three fresh animal drugs, i.e. Shougong (Peking gecko, Gekko swinhonis), Qi She (sharp-snouted pitviper, Deinagkistrodon acutus), and Jinqian Baihua She (many-banded krait, Bungarus multicinctus)] as an example, we established a qPCR assay for Qi She in the capsule, which verified the feasibility of the quality control method based on molecular quantification. Species-specific primers and TaqMan probe for Qi She were designed, and the qPCR assay system was then established. The assay exhibited a good specificity; there’s a good linearity between Ct values and logarithm of the target amplicon copy numbers within the range of 8.8 × 101 to 8.8 × 106 copies/μL, and the limit of detection was 88 copies/μL. The method was validated through reproducibility, stability assessment. Recovery of spiked samples was between 91.59% and 101.69%. It was verified that the copy numbers reflected the original feeding amount of an animal-derived crude drug by self-made Jinlong capsules. The assay was successfully applied in Qi She-specific amplicon determination in 20 batches of Jinlong capsule. The study was expected to provide a new strategy for quality control of CPM containing animal-derived crude drug.

Comparison of Methods for the Estimation of the Maximum Oxygen Uptake of Men Drug Addicts.

Background: Maximum oxygen uptake (VO2max) is an important respiratory physiological index of the aerobic endurance of the body, especially for special groups such as drug addicts, and it is an important indicator for assessing the cardiopulmonary function and formulating exercise prescriptions. Although the cardiopulmonary exercise test (CPX) is a classic method to directly measure VO2max, this method is limited by factors such as cumbersome operating procedures and expensive equipment, resulting in its relatively low applicability. Recently, many studies have begun to focus on the estimation of VO2max in different groups of people, but few studies have focused on drug addicts.Methods: Fifteen chemically synthesized drug addicts (such as amphetamines) and Fifteen plant-derived drug addicts (such as heroin) were recruited at the Chongqing Compulsory Isolation and Drug Rehabilitation Center in China. First, the VO2max of subjects was directly measured through the CPX. Second, after subjects were fully rested, they were required to complete the 30-s high-leg raise, 1,000-m walk, and 3-min step experiment. Finally, SPSS 21.0 software was used to perform the correlation and linear regression analysis to verify the estimated effectiveness.Results: (1) Regardless of chemically synthesized or natural plant-derived drug addicts, the years of drug use and walking time of 1,000 m were significantly negatively correlated with VO2max (chemically synthesized: P < 0.01 and natural plant-derived: P < 0.05), the number of 30-s high-leg raises was a significantly positive correlation with VO2max (P < 0.05 and P < 0.01), and the 3-min step index was significantly positively correlated with VO2max (P < 0.01 and P < 0.01). (2) Regression analysis shows that the 30-s high-leg lift, 1,000-m walking, and 3-min step experiment could effectively estimate the VO2max of chemically synthesized and natural plant-derived drug addicts. (3) Multiple linear regression constructed by the years of drug use combined with the step index has the highest estimated accuracy for the VO2max of chemically synthesized drug addicts (96.48%), while the unary regression equation established by a single step index has the highest prediction accuracy for the VO2max of natural plant-derived addicts (94.30%).Conclusion: The indirect measurement method could effectively estimate the VO2max of drug addicts, but different measurement methods have certain differences in the estimation accuracy of VO2max of different drug addicts. In the future, the physical characteristics of drug users can be fully considered, combined with more cutting-edge science and technology, to make the estimation accuracy of VO2max closer to the real level.

Arsenene Nanodots with Selective Killing Effects and their Low‐Dose Combination with ß‐Elemene for Cancer Therapy (Adv. Mater. 37/2021)

Arsenical Drugs In article number 2102054, Aiguo Wu, Tian Xie, Wei Tao, and co-workers reveal PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity and negligible systemic toxicity as a new-concept arsenical drug. This AsNDs@PEG, when applied in a low-dose combination strategy with β-elemene, a plant-derived anticancer drug, achieves synergistic therapeutic outcomes.

Recent Advances in Paclitaxel-based Self-Delivery Nanomedicine for Cancer Therapy.

Paclitaxel (PTX) is the first natural plant-derived chemotherapeutic drug approved by the Food and Drug Administration. However, the clinical applications of PTX are limited by some drawbacks, such as poor water solubility, rapid blood clearance, nonspecific distribution, and adverse side effects. Nanocarriers have made important contributions to drug delivery and cancer therapy in recent years. However, low drug loading capacity, nanocarrier excipients-induced toxicity or immunogenicity, and complicated synthesis technologies pose a challenge for the clinical application of nanocarriers. To address these issues, the self-delivery nanomedicine (SDNs), in which pure drug molecules directly self-assemble into nanomedicine, have been developed for drug delivery and enhancing antitumor efficacy. In this review, we comprehensively summarize the recent advances in PTX-based SDNs for cancer therapy. First, the self-assembly strategies to develop pure PTX nanodrugs are discussed. Then, the emerging strategies of co-assembly PTX and other therapeutic agents for effective combination therapy are presented, composing of combination chemotherapy, chemo-photothermal therapy, chemo-photodynamic therapy, chemo-immunotherapy, and chemo-gene therapy. Finally, the limitations and future outlook of SDNs are discussed. The rational design of these unique nanoplatforms may make a new direction to develop highly efficient drug delivery systems for cancer therapy.

Potential Role of In Vitro-In Vivo Correlations (IVIVC) for the Development of Plant-Derived Anticancer Drugs.

Conventional medicines, along with herbal formulations of Chinese, serve as the primary source and hub of active new drugs where the initial research concentrates on the extraction and isolation of bioactive lead compound(s) to treat several diseases largely for cancer. Plant-derived natural products and their analogs reveal a significant source of several clinically useful anticancer agents. Herbs and herbal derived active compounds play an unavoidable role in the treatment, drug discovery and delivery for decades, as evidenced by numerous existing marked drugs and various cancer-related molecular targets in clinical development. Solubility, resistance and metabolic limitations of the drug can be overcome by suitable molecular modifications. Due to enhancements in tumor targeting technology, some agents who failed in earlier clinical studies are also stimulating renewed interest. In this connection, In Vitro-In Vivo Correlation (IVIVC) plays an important role in the development of dosage forms in the field of pharmaceutical technology. IVIVC tool fastens and improves the drug development process and product quality, which is also utilized in internal control for scale-up to improve formulations and alternative production processes. Most importantly, this IVIVC tool lessens the number of human studies during new pharmaceuticals developments. In this review, we would like to grab the attention of readers to the importance and significance of IVIVC for natural products of anticancer drugs examples such as Docetaxel, Etoposide phosphate, 6-Gingerol, Capsaicin, etc.

Arsenene Nanodots with Selective Killing Effects and their Low-Dose Combination with ß-Elemene for Cancer Therapy.

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell-cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi-drug combination strategy with β-elemene, a plant-derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on-demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large-scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new-concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

Cytochrome P450 Enzymes as Key Drivers of Alkaloid Chemical Diversification in Plants.

Plants produce more than 20,000 nitrogen-containing heterocyclic metabolites called alkaloids. These chemicals serve numerous eco-physiological functions in the plants as well as medicines and psychedelic drugs for human for thousands of years, with the anti-cancer agent vinblastine and the painkiller morphine as the best-known examples. Cytochrome P450 monooxygenases (P450s) play a key role in generating the structural variety that underlies this functional diversity of alkaloids. Most alkaloid molecules are heavily oxygenated thanks to P450 enzymes’ activities. Moreover, the formation and re-arrangement of alkaloid scaffolds such as ring formation, expansion, and breakage that contribute to their structural diversity and bioactivity are mainly catalyzed by P450s. The fast-expanding genomics and transcriptomics databases of plants have accelerated the investigation of alkaloid metabolism and many players behind the complexity and uniqueness of alkaloid biosynthetic pathways. Here we discuss recent discoveries of P450s involved in the chemical diversification of alkaloids and how these inform our approaches in understanding plant evolution and producing plant-derived drugs.

Identification of the Trace Components in BopuzongJian and Macleaya cordata Extract Using LC-MS Combined with a Screening Method.

Bopu powder® and Sangrovit® were developed from Macleaya cordata and are widely used in agriculture and animal husbandry, but their impurities have been rarely reported in the literature. Impurity analysis is of great importance to the quality and safety of veterinary drugs. In this study, high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with a screening method was used to screen and characterize the impurities in Bopu powder® and Sangrovit®. A total of 58 impurities were screened from Bopu powder® and Sangrovit® using the screening strategies, of which 39 were identified by their accurate m/z value, characteristic MS/MS data, and fragmentation pathways of references. This established method was used for impurity analysis for the first time and proved to be a useful and rapid tool to screen and identify the impurities of Bopu powder® and Sangrovit®, especially for those at trace levels in a complex sample. In addition, this study marks the first comprehensive research into impurities in these two products and has great significance for the systematic detection of impurities in other plant-derived drugs.

Gundelia tournefortii: Fractionation, Chemical Composition and GLUT4 Translocation Enhancement in Muscle Cell Line.

Type 2 diabetes (T2D) is a chronic metabolic disease, which could affect the daily life of patients and increase their risk of developing other diseases. Synthetic anti-diabetic drugs usually show severe side effects. In the last few decades, plant-derived drugs have been intensively studied, particularly because of a rapid development of the instruments used in analytical chemistry. We tested the efficacy of Gundelia tournefortii L. (GT) in increasing the translocation of glucose transporter-4 (GLUT4) to the myocyte plasma membrane (PM), as a main strategy to manage T2D. In this study, GT methanol extract was sub-fractionated into 10 samples using flash chromatography. The toxicity of the fractions on L6 muscle cells, stably expressing GLUTmyc, was evaluated using the MTT assay. The efficacy with which GLUT4 was attached to the L6 PM was evaluated at non-toxic concentrations. Fraction 6 was the most effective, as it stimulated GLUT4 translocation in the absence and presence of insulin, 3.5 and 5.2 times (at 250 μg/mL), respectively. Fraction 1 and 3 showed no significant effects on GLUT4 translocation, while other fractions increased GLUT4 translocation up to 2.0 times. Gas chromatography–mass spectrometry of silylated fractions revealed 98 distinct compounds. Among those compounds, 25 were considered anti-diabetic and glucose disposal agents. These findings suggest that GT methanol sub-fractions exert an anti-diabetic effect by modulating GLUT4 translocation in L6 muscle cells, and indicate the potential of GT extracts as novel therapeutic agents for T2D.

PLANT-DERIVED CHEMOTHERAPEUTICS DRUGS FOR CANCER CHEMOTHERAPY

Cancer chemotherapeutic drugs acts in different manner to kill malignant cells. Most of the anticancer drugs available in clinical practice to treat cancer patients, are natural products including whole plant extract, crude plant extracts, isolated constituents, plant –based drug formulations etc. These natural compounds have been a basis for the development of several drugs against cancer. Agents such as topotecan, taxol, vinca alkaloids (vincristine, vinblastine, vinorelbine and vindesine), are important anticancer agents in widespread clinical use. Other agents, such as combretastatin, flavopiridol, betulinic acid were shown to have anti-tumor effects in both in vitro and in vivo experiments.&#x0D; In this review, we aim to make a brief description of classical plant-derived chemotherapeutics drugs and also to highlight the importance of these natural compounds in the development of new potential drugs in cancer treatment.

Plumbagin Elicits Cell-Specific Cytotoxic Effects and Metabolic Responses in Melanoma Cells.

Melanoma is one of the most malignant skin cancers that require comprehensive therapies, including chemotherapy. A plant-derived drug, plumbagin (PLB), exhibits an anticancer property in several cancers. We compared the cytotoxic and metabolic roles of PLB in A375 and SK-MEL-28 cells, each with different aggressiveness. In our results, they were observed to have distinctive mitochondrial respiratory functions. The primary reactive oxygen species (ROS) source of A375 can be robustly attenuated by cell membrane permeabilization. A375 cell viability and proliferation, migration, and apoptosis induction are more sensitive to PLB treatment. PLB induced metabolic alternations in SK-MEL-28 cells, which included increasing mitochondrial oxidative phosphorylation (OXPHOS), mitochondrial ATP production, and mitochondrial mass. Decreasing mitochondrial OXPHOS and total ATP production with elevated mitochondrial membrane potential (MMP) were observed in PLB-induced A375 cells. PLB also induced ROS production and increased proton leak and non-mitochondria respiration in both cells. This study reveals the relationship between metabolism and cytotoxic effects of PLB in melanoma. PLB displays stronger cytotoxic effects on A375 cells, which exhibit lower respiratory function than SK-MEL-28 cells with higher respiratory function, and triggers cell-specific metabolic changes in accordance with its cytotoxic effects. These findings indicate that PLB might serve as a promising anticancer drug, targeting metabolism.