Hepatoprotective Potential of Malaysian Medicinal Plants: A Review on Phytochemicals,Oxidative Stress,and Antioxidant Mechanisms

Hepatotoxicity is a major global public health concern. Despite advances in modern medicine, the demerits of chemically prepared drugs outweigh their merits. In addition, the treatment of liver diseases based on modern medical principles has been found to produce several undesired side effects. Therefore, the exploration of medicinal plants has gained worldwide attention for treating various diseases, including liver diseases, owing to their potential efficacy and cost effectiveness. Several plants, including Andrographis paniculata, Bauhinia purpurea, Commelina nudiflora, Dillenia suffruticosa, Elaeis guineensis, Lygodium microphyllum, and Nephrolepis biserrata, have been reported with hepatoprotection. Moreover, these plants have been shown to play a vital role in ameliorating cellular damage because they contain several phytochemicals, including alkaloids, saponins, flavonoids, tannins, terpenoids, steroids, polyphenols, and diterpenoid lactones. The following antioxidant, anti-inflammatory, immunomodulatory, and hepatoprotective compounds have been found in these plants: andrographolide, rosmarinic acid, phenol, eugenol, 9,12-octadecadienoic, n-hexadecanoic acid, dihydroxy dimethoxy flavone, sitosterol, demethoxycurcumin, quercetin, linoleic acid, stigmasterol, kojic acid, indole-2-one, α-terpinol, linalool, kaempferol, catechin, ellagic acid, and oleanolic acid. This paper aimed to provide an in-depth review of in vivo studies on Malaysian medicinal plants possessing hepatoprotective properties, phytochemical ingredients, and antioxidant mechanisms, with an emphasis on the species proven particularly useful for treating hepatic disorders.     

Imperata cylindrica: A Review of Phytochemistry,Pharmacology, and Industrial Applications

Imperata cylindrica is a medicinal plant native to southwestern Asia and the tropical and subtropical zones. To date, 72 chemical constituents have been isolated and identified from I. cylindrica Among these compounds, saponins, flavonoids, phenols, and glycosides are the major constituents. Investigations of pharmacological activities of I. cylindrica revealed that this edible medicinal herb exhibits a wide range of therapeutic potential including immunomodulatory, antibacterial, antitumor, anti-inflammatory, and liver protection activities both in vivo and in vitro. The purpose of this review is to provide an overview of I. cylindrica studies until 2019. This article also intends to review advances in the botanical, phytochemical, and pharmacological studies and industrial applications of I. cylindrica, which will provide a useful bibliography for further investigations and applications of I. cylindrica in medicines and foods.     

Synthesis and immunological evaluation of Mincle ligands-based antitumor vaccines

The development of novel adjuvants constitutes a new strategy for the research of tumor vaccines. Immunomodulatory molecule adjuvants are one of the novel adjuvants that can effectively stimulate the pattern recognition receptors to activate the downstream pathways of immune cells. However, there are few studies on immunomodulatory molecular adjuvants associated with C-type lectin. It has been reported that GlcC₁₄C₁₈ is a Mincle ligand with a relatively simple structure and strong adjuvant activity in vivo. Herein, we coupled GlcC₁₄C₁₈ with MUC1 glycopeptide and evaluated its immune effect. In addition, we also synthesized α-GlcC₁₄C₁₈-MUC1 and β-GlcC₁₄C₁₈-MUC1 based on the two configurations of GlcC₁4C₁₈ and compared their immune effects. The results show that both of the two configurations of the vaccine have a good immune effect, but to a certain extent, the immune effect of β-GlcC₁₄C₁₈-MUC1 is better than that of α-GlcC₁₄C₁₈-MUC1.     

The Phytochemistry and Pharmacology of Tulbaghia,Allium, Crinum and Cyrtanthus: ‘Talented’ Taxa from the Amaryllidaceae

Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera Allium, Tulbaghia, Cyrtanthus and Crinum biosynthesize novel alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and immunomodulatory effects. Traditionally, natural products from Amaryllidaceae are utilized to treat non-communicable and infectious human diseases. Galanthamine, a drug from this family, is clinically relevant in treating the neurocognitive disorder, Alzheimer’s disease, which underscores the importance of the Amaryllidaceae alkaloids. Although Amaryllidaceae provide a plethora of biologically active compounds, there is tardiness in their development into clinically pliable medicines. Other genera, including Cyrtanthus and Tulbaghia, have received little attention as potential sources of promising drug candidates. Given the reciprocal relationship of the increasing burden of human diseases and limited availability of medicinal therapies, more rapid drug discovery and development are desirable. To expedite clinically relevant drug development, we present here evidence on bioactive compounds from the genera Allium, Tulgbaghia, Cyrtanthus and Crinum and describe their traditional and pharmacological applications.     

Proteomic Research on the Antitumor Properties of Medicinal Mushrooms

Medicinal mushrooms are increasingly being recognized as an important therapeutic modality in complementary oncology. Until now, more than 800 mushroom species have been known to possess significant pharmacological properties, of which antitumor and immunomodulatory properties have been the most researched. Besides a number of medicinal mushroom preparations being used as dietary supplements and nutraceuticals, several isolates from mushrooms have been used as official antitumor drugs in clinical settings for several decades. Various proteomic approaches allow for the identification of a large number of differentially regulated proteins serendipitously, thereby providing an important platform for a discovery of new potential therapeutic targets and approaches as well as biomarkers of malignant disease. This review is focused on the current state of proteomic research into antitumor mechanisms of some of the most researched medicinal mushroom species, including Phellinus linteus, Ganoderma lucidum, Auricularia auricula, Agrocybe aegerita, Grifola frondosa, and Lentinus edodes, as whole body extracts or various isolates, as well as of complex extract mixtures.     

<Emphasis Type="Italic">L</Emphasis>-Carnitine,Immunomodulation, and Human Immunodeficiency Virus (HIV)-related Disorders

Summary. The use of pharmacologic doses of the conditionally-essential nutrient L-carnitine (LC) has been associated with positive effects on the immune system. We have recently suggested that this property of LC could be mediated through activation of the glucocorticoid receptor alpha. Human immunodeficiency virus (HIV)-infected individuals, especially those on antiretroviral therapy, may become LC-deficient. This evidence, together with the immunomodulatory properties of LC, its known major role in lipid and energy metabolisms, and its proposed antiapoptotic and neuroprotective actions, have encouraged the use of LC supplementation as a potential treatment for HIV-related disorders, such as lipodystrophy and peripheral neuropathy. Preliminary results, mostly from small-scale uncontrolled studies are conflicting, whilst larger controlled trials are warranted.     

Bioactivities of the Genus <em>Combretum</em> (Combretaceae): A Review

The Combretaceae is a large family of herbs, shrubs and trees, comprising about 20 genera and 600 species with tropical distribution around the globe and centers of diversity in Africa and Asia. Some Combretum species are extensively used in traditional medicine against inflammation, infections, diabetes, malaria, bleeding, diarrhea and digestive disorders and others as a diuretic. The present work is a literature survey of Combretum species that have been evaluated for their ability to exert biological activities. A total number of 36 Combretum species are discussed with regard to plant parts used, component tested and bioassay models. This review is of fundamental importance to promoting studies on Combretum species, thereby contributing to the development of new therapeutic alternatives that may improve the health of people suffering from various health problems.     

Identification and Determination of <em>Aconitum</em> Alkaloids in <em>Aconitum</em> Herbs and <em>Xiaohuoluo Pill</em> Using UPLC-ESI-MS

A rapid, specific, and sensitive ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) method to examine the chemical differences between Aconitum herbs and processed products has been developed and validated. Combined with chemometrics analysis of principal component analysis (PCA) and orthogonal projection to latent structural discriminate analysis, diester-diterpenoid and monoester-type alkaloids, especially the five alkaloids which contributed to the chemical distinction between Aconitum herbs and processed products, namely mesaconitine (MA), aconitine (AC), hypaconitine (HA), benzoylmesaconitine (BMA), and benzoylhypaconitine (BHA), were picked out. Further, the five alkaloids and benzoylaconitine (BAC) have been simultaneously determined in the Xiaohuoluo pill. Chromatographic separations were achieved on a C₁₈ column and peaks were detected by mass spectrometry in positive ion mode and selected ion recording (SIR) mode. In quantitative analysis, the six alkaloids showed good regression, (r) > 0.9984, within the test ranges. The lower limit quantifications (LLOQs) for MA, AC, HA, BMA, BAC, and BHA were 1.41, 1.20, 1.92, 4.28, 1.99 and 2.02 ng·mL^-1, respectively. Recoveries ranged from 99.7% to 101.7%. The validated method was applied successfully in the analysis of the six alkaloids from different samples, in which significant variations were revealed. Results indicated that the developed assay can be used as an appropriate quality control assay for Xiaohuoluo pill and other herbal preparations containing Aconitum roots.     

The Effectiveness of Rhodiola rosea L. Preparations in Alleviating Various Aspects of Life-Stress Symptoms and Stress-Induced Conditions—Encouraging Clinical Evidence

Rhodiola rosea L. has a long history of use in traditional medicine to stimulate the nervous system, treat stress-induced fatigue and depression, enhance physical performance and work productivity and treat gastrointestinal ailments and impotence. Apart from its well-established traditional use, a significant number of publications on the clinical efficacy of various R. rosea preparations can be found in the literature. The majority of these studies are related to the efficacy of R. rosea in terms of cognitive functions and mental performance, including various symptoms of life-stress, fatigue and burnout. The beneficial effects of this medicinal plant on enhancing physical performance have also been evaluated in professional athletes and non-trained individuals. Moreover, even though most evidence originates from pre-clinical trials, several clinical studies have additionally demonstrated the remediating effects of R. rosea on cardiovascular and reproductive health by addressing non-specific stress damage and reversing or healing the disrupted physiologies and disfunctions. Overall, in accordance with its aim, the results presented in this review provide an encouraging basis for the clinical efficacy of R. rosea preparations in managing various aspects of stress-induced conditions.     

Artemisia abrotanum L. (Southern Wormwood)—History,Current Knowledge on the Chemistry,Biological Activity,Traditional Use and Possible New Pharmaceutical and Cosmetological Applications

Artemisia abrotanum L. (southern wormwood) is a plant species with an important position in the history of European and Asian medicine. It is a species famous as a medicinal plant in Central Asia, Asia Minor, and in South-East and Central Europe. The raw materials obtained from this species are Abrotani herba and Abrotani folium. In the traditional European medicine, they have been used successfully most of all in liver and biliary tract diseases, in parasitic diseases in children and as antipyretic medication. In the official European medicine, this plant species is recommended by the French Pharmacopoeia for use in homeopathy. In many European countries, it is used traditionally in allopathy. The latest studies on the biological activity of extracts from the aboveground parts of the plant and/or the leaves, and/or the essential oil have provided evidence of other possible applications related to their antibacterial, antifungal, antioxidant, anticancer, and antiallergic properties. The latest studies have also focused on the repellent activity of the essential oil of this species and the possibility to use it in the prevention of diseases in which insects are the vectors. The main substances obtained from the plant that are responsible for this activity are: the essential oil, coumarins, phenolic acids, and flavonoids. Some of the latest investigations emphasize the large differences in the composition of the essential oil, determined by the geographical (climatic) origin of the plant. A. abrotanum is recommended by the European Cosmetic Ingredients Database (CosIng) as a source of valuable cosmetic ingredients. Additionally, the leaves of this species possess a well-established position in the food industry. This plant species is also the object of biotechnological studies.     

The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation

In the last 10 years, mesenchymal stem cells (MSCs) have emerged as a therapeutic approach to regenerative medicine, cancer, autoimmune diseases, and many more due to their potential to differentiate into various tissues, to repair damaged tissues and organs, and also for their immunomodulatory properties. Findings in vitro and in vivo have demonstrated immune regulatory function of MSCs and have facilitated their application in clinical trials, such as those of autoimmune diseases and chronic inflammatory diseases. There has been an increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation (HSCT), including hematopoietic stem cell engraftment and the prevention and treatment of graft-versus-host disease (GVHD), and their therapeutic potential has been reported in numerous clinical trials. Although the safety of clinical application of MSCs is established, further modifications to improve their efficacy are required. In this review, we summarize advances in the potential use of MSCs in HSCT. In addition, we discuss their use in clinical trials of the treatment of GVHD following HSCT, the immunomodulatory capacity of MSCs, and their regenerative and therapeutic potential in the field of HSCT.     

Functionalization of Pasteurized Milk Using Rosemary,Thyme, and Ammoides Aqueous Extracts for Better Microbial Quality and an Improved Antioxidant Activity

This study aimed to evaluate the effects of thyme (Thymus vulgaris L.), rosemary (Rosmarinus officinalis L.), and ammoides (Ammoidespusilla L.) aqueous extracts supplementation on the quality of heat-treated (55, 65, and 75 °C) raw milk (sample lots: A, B, and C) and cold-stored pasteurized milk (lot D). The three herbs have shown rich polyphenol contents (32.65–104.23 mgGAE/g), relevant antioxidant capacity, and high caffeic and rosmarinic acids and catechin contents. A significant reduction in psychrotrophic and total viable bacteria counts (PC and TVC) was attained following milk extract supplementation in both experiments. Monitoring PC and TVC counts in sample lots (A, B, and C) has revealed a significant improvement in extracts’ effectiveness in reducing the TVC count with the increment of temperature. The highest reductions of PC and TVC counts were achieved, respectively, in samples treated with thyme and rosemary in (lots: A, B, and C) and in samples treated with ammoides and thyme in (lot D). Thyme extract showed the highest milk serum DPPH scavenging activity (74.84% at 0.1 mg/mL) and induced a significant Listeria monocytogenes growth inhibition (>1 Log cycle). The sensory evaluation of supplemented milk has shown good consumer acceptability of ammoides-supplemented milk, quite similar to the control sample.     

A capsule review of recent studies on the application of mass spectrometry in the analysis of Chinese medicinal herbs

Chinese herbal medicine is gaining increasing popularity worldwide as an alternative approach to the development of pharmaceuticals in therapeutic applications. Chemical characterization and compositional analysis of Chinese medicines provide the necessary scientific basis for the discovery and development of new drugs of natural origin. Applications of mass spectrometry in the analysis of Chinese herbal medicines have been growing rapidly in recent years owing to the rapid technical advances and increasing availability of the instrumentation. This paper reviews the current status of how different mass spectrometric techniques are being used to support research studies of Chinese medicines. The focus is on crude herbal medicines and their derived products. The review is not meant to be exhaustive, but rather to provide a general overview of the various research activities in this rapidly expanding field. In the discussion of specific herbs, the emphasis is placed on ginseng and Danshen, two of the herbs for which active experimental work is on-going in the authors' laboratories. Other selected herbs will be discussed only briefly, aiming primarily to illustrate the current status of research in the area.     

Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine

Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated with MSC response. The anti-inflammatory and immunomodulatory capacity of MSC may be paramount in the restoration of localized or systemic conditions for normal healing and tissue regeneration. Allogeneic MSC treatments, categorized as a drug by regulatory agencies, have been widely pursued, but new studies demonstrate the efficacy of autologous MSC therapies, even for individuals affected by a disease state. Safety and regulatory concerns surrounding allogeneic cell preparations make autologous and minimally manipulated cell therapies an attractive option for many regenerative, anti-inflammatory and autoimmune applications.     

Mycomedicine: A Unique Class of Natural Products with Potent Anti-tumour Bioactivities

Mycomedicine is a unique class of natural medicine that has been widely used in Asian countries for thousands of years. Modern mycomedicine consists of fruiting bodies, spores, or other tissues of medicinal fungi, as well as bioactive components extracted from them, including polysaccharides and, triterpenoids, etc. Since the discovery of the famous fungal extract, penicillin, by Alexander Fleming in the late 19th century, researchers have realised the significant antibiotic and other medicinal values of fungal extracts. As medicinal fungi and fungal metabolites can induce apoptosis or autophagy, enhance the immune response, and reduce metastatic potential, several types of mushrooms, such as Ganoderma lucidum and Grifola frondosa, have been extensively investigated, and anti-cancer drugs have been developed from their extracts. Although some studies have highlighted the anti-cancer properties of a single, specific mushroom, only limited reviews have summarised diverse medicinal fungi as mycomedicine. In this review, we not only list the structures and functions of pharmaceutically active components isolated from mycomedicine, but also summarise the mechanisms underlying the potent bioactivities of several representative mushrooms in the Kingdom Fungi against various types of tumour.     

Characterization of Bioactive Compounds from Acacia concinna and Citrus limon,Silver Nanoparticles’ Production by A. concinna Extract,and Their Biological Properties

The applications of bioactive compounds from medicinal plants as therapeutic drugs are largely increasing. The present study selected the bioactive compounds from Acacia concinna (A. concinna) and Citrus limon (C. limon) to assess their phytochemicals, proteins, and biological activity. The plant material was collected, and extraction performed as per the standard procedure. Qualitative analysis was undertaken, and identification of functional organic groups was performed by FTIR and HPLC. Antibacterial, anticancer, antioxidant, antihyperglycemic, antihyperlipidemic, and inhibition kinetics studies for enzymes were performed to assess the different biological activities. Flavonoids and phenols were present in a significant amount in both the selected plants. A. concinna showed significant antimicrobial activity against Z. mobilis, E. coli, and S. aureus, with minimum inhibition zones (MIZ) of 24, 22, and 20 mm, respectively. C. limon strongly inhibited all the tested pathogenic bacteria with maximum and minimum MIZ of 32 and 17 mm. A. concinna silver nanoparticles also exhibited potent antimicrobial activity. Both extracts showed substantial antioxidant, antihyperlipidemic, antidiabetic, anticancer (MCF-7), and anti-urease (antiulcer) properties. To conclude, these plants can be used to treat hyperlipidemia, diabetes, cancer, and gastrointestinal ulcers. They can also serve as antimicrobial and antioxidant agents. Thus, the studied plants must be exploited cost-effectively to generate therapeutic drugs for various diseases.     

Zingiber officinale var. rubrum: Red Ginger’s Medicinal Uses

Zingiber officinale var. rubrum (red ginger) is widely used in traditional medicine in Asia. Unlike other gingers, it is not used as a spice in cuisines. To date, a total of 169 chemical constituents have been reported from red ginger. The constituents include vanilloids, monoterpenes, sesquiterpenes, diterpenes, flavonoids, amino acids, etc. Red ginger has many therapeutic roles in various diseases, including inflammatory diseases, vomiting, rubella, atherosclerosis, tuberculosis, growth disorders, and cancer. Scientific evidence suggests that red ginger exhibits immunomodulatory, antihypertensive, antihyperlipidemic, antihyperuricemic, antimicrobial, and cytotoxic activities. These biological activities are the underlying causes of red ginger’s therapeutic benefits. In addition, there have been few reports on adverse side effects of red ginger. This review aims to provide insights in terms the bioactive constituents and their biosynthesis, biological activities, molecular mechanisms, pharmacokinetics, and qualitative and quantitative analysis of red ginger.     

L-Carnitine, Immunomodulation, and Human Immunodeficiency Virus (HIV)-related Disorders

The use of pharmacologic doses of the conditionally-essential nutrient L-carnitine (LC) has been associated with positive effects on the immune system. We have recently suggested that this property of LC could be mediated through activation of the glucocorticoid receptor alpha. Human immunodeficiency virus (HIV)-infected individuals, especially those on antiretroviral therapy, may become LC-deficient. This evidence, together with the immunomodulatory properties of LC, its known major role in lipid and energy metabolisms, and its proposed antiapoptotic and neuroprotective actions, have encouraged the use of LC supplementation as a potential treatment for HIV-related disorders, such as lipodystrophy and peripheral neuropathy. Preliminary results, mostly from small-scale uncontrolled studies are conflicting, whilst larger controlled trials are warranted.     

The Genus Miconia Ruiz & Pav. (Melastomataceae): Ethnomedicinal Uses,Pharmacology, and Phytochemistry

Species of the genus Miconia are used in traditional medicine for the treatment of diseases, such as pain, throat infections, fever, and cold, and they used as depuratives, diuretics, and sedatives. This work reviewed studies carried out with Miconia species, highlighting its ethnomedicinal uses and pharmacological and phytochemical potential. This information was collected in the main platforms of scientific research (PubMed, Scopus, and Web of Science). Our findings show that some of the traditional uses of Miconia are corroborated by biological and/or pharmacological assays, which demonstrated, among other properties, anti-inflammatory, analgesic, antimutagenic, antiparasitic, antioxidant, cytotoxic, and antimicrobial activities. A total of 148 chemical compounds were identified in Miconia species, with phenolic compounds being the main constituents found in the species of this genus. Such phytochemical investigations have demonstrated the potential of species belonging to this genus as a source of bioactive substances, thus reinforcing their medicinal and pharmacological importance.     

Macrocyclic [N<Subscript>5</Subscript>] transition metal complexes: synthesis,characterization and biological activities

Novel penta-azamacrocyclic 21-membered [N₅] ligand [L] and its transition metal complexes with Co(II), Ni(II), Cu(II), Ru(III) and Pd(II) have been isolated and characterized. The mode of bonding and overall geometry of the complexes have been inferred through IR, MS, UV–Vis, EPR, ¹H NMR spectral studies, molar conductivity, magnetic, thermal and microanalyses, On the basis of above studies, an octahedral geometry has been proposed for all complexes except Pd(II) chloride complex which adopt square planar geometry. The in vitro antitumor activity of the synthesized ligand and some selected complexes against human breast and human hepatocarcinoma cell lines (MCF-7) and (HePG2), respectively has been studied. The results show that the tested compounds are potent antitumor agents. Also the ligand and some selected complexes have been tested for their inhibitory effect on the growth of bacteria: Streptococcus pyogenes as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria. The activity data show that most of the tested compounds exhibit remarkable antibacterial activity against these organisms.