Plant-derived Secondary Metabolites Research Articles

The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer's disease: a narrative review.

Alzheimer's disease is a neurodegenerative disease that affects a large proportion of older adult people and is characterized by memory loss, progressive cognitive impairment, and various behavioral disturbances. Although the pathological mechanisms underlying Alzheimer's disease are complex and remain unclear, previous research has identified two widely accepted pathological characteristics: extracellular neuritic plaques containing amyloid beta peptide, and intracellular neurofibrillary tangles containing tau. Furthermore, research has revealed the significant role played by neuroinflammation over recent years. The inflammatory microenvironment mainly consists of microglia, astrocytes, the complement system, chemokines, cytokines, and reactive oxygen intermediates; collectively, these factors can promote the pathological process and aggravate the severity of Alzheimer's disease. Therefore, the development of new drugs that can target neuroinflammation will be a significant step forward for the treatment of Alzheimer's disease. Flavonoids are plant-derived secondary metabolites that possess various bioactivities. Previous research found that multiple natural flavonoids could exert satisfactory treatment effects on the neuroinflammation associated with Alzheimer's disease. In this review, we describe the pathogenesis and neuroinflammatory processes of Alzheimer's disease, and summarize the effects and mechanisms of 13 natural flavonoids (apigenin, luteolin, naringenin, quercetin, morin, kaempferol, fisetin, isoquercitrin, astragalin, rutin, icariin, mangiferin, and anthocyanin) derived from plants or medicinal herbs on neuroinflammation in Alzheimer's disease. As an important resource for the development of novel compounds for the treatment of critical diseases, it is essential that we focus on the exploitation of natural products. In particular, it is vital that we investigate the effects of flavonoids on the neuroinflammation associated with Alzheimer's disease in greater detail.

Optical Characteristics of Silver Nanoparticles Obtained Using Artemisia tilesii Ledeb. "Hairy" Root Extracts With High Flavonoid Content

Background. "Hairy" roots can be used for production of plant-derived secondary metabolites, such as flavonoids, which have antioxidant and reducing properties. It seems promising to use the process of silver nanoparticles formation as a method of determining the level of reducing power. This approach allows simul­taneously to obtain nanoparticles with different biological activity and evaluate the reducing potential of dif­ferent plants. Objective. The aim of the study was to determine the dependence of optical properties (ultraviolet/visible spectroscopy, UV-Vis spectra) of solutions of silver nanoparticles obtained using wormwood "hairy" root extracts on the content of flavonoids as compounds with reducing activity. Methods. Four Artemisia tilesii “hairy” root lines from the collection of the Institute of Cell Biology and Genetic Engineering NAS of Ukraine were grown for five weeks in liquid 1/2 MS medium with 20 g/l sucrose. "Hairy" roots were homogenized in 70% ethanol, the extracts were centrifuged, total flavonoid content was determined, and extracts were used for the silver nanoparticles preparation via reduction of Ag+ to Ag0 from AgNO3. UV-Vis spectra at 300–600 nm range were recorded right after colloid solution preparation, in five, and in nine days. Results. Total flavonoid content varied from 4.01 ± 0.39 to 15.37 ± 1.08 mg RE/g FW. The UV-Vis spectra curves of absorption increased with the course of time, mostly from day 0 to day 5. At this period, absorption at 370–500 nm wavelength increased almost twofold. The peak absorption of all samples was detected at 440 nm, and the maximum values at the wavelength of 440 nm correlated with the content of flavonoids. This correlation did not change over time. Conclusions. The optical properties of silver nanoparticles colloid solutions obtained using A. tilesii "hairy" root extracts correlated with the total flavonoid content of the samples. Even though the absorbance of the colloid solutions increased with time, those increases correlated with flavonoid content as well. The determination of the optical properties of AgNPs colloid solution can be used as a convenient way of quickly comparing the reducing ability of extracts both right after the formation of a colloidal solution and after some time of its storage.

Plant Metabolomics: An Overview of the Role of Primary and Secondary Metabolites against Different Environmental Stress Factors

Several environmental stresses, including biotic and abiotic factors, adversely affect the growth and development of crops, thereby lowering their yield. However, abiotic factors, e.g., drought, salinity, cold, heat, ultraviolet radiations (UVr), reactive oxygen species (ROS), trace metals (TM), and soil pH, are extremely destructive and decrease crop yield worldwide. It is expected that more than 50% of crop production losses are due to abiotic stresses. Moreover, these factors are responsible for physiological and biochemical changes in plants. The response of different plant species to such stresses is a complex phenomenon with individual features for several species. In addition, it has been shown that abiotic factors stimulate multi-gene responses by making modifications in the accumulation of the primary and secondary metabolites. Metabolomics is a promising way to interpret biotic and abiotic stress tolerance in plants. The study of metabolic profiling revealed different types of metabolites, e.g., amino acids, carbohydrates, phenols, polyamines, terpenes, etc, which are accumulated in plants. Among all, primary metabolites, such as amino acids, carbohydrates, lipids polyamines, and glycine betaine, are considered the major contributing factors that work as osmolytes and osmoprotectants for plants from various environmental stress factors. In contrast, plant-derived secondary metabolites, e.g., phenolics, terpenoids, and nitrogen-containing compounds (alkaloids), have no direct role in the growth and development of plants. Nevertheless, such metabolites could play a significant role as a defense by protecting plants from biotic factors such as herbivores, insects, and pathogens. In addition, they can enhance the resistance against abiotic factors. Therefore, metabolomics practices are becoming essential and influential in plants by identifying different phytochemicals that are part of the acclimation responses to various stimuli. Hence, an accurate metabolome analysis is important to understand the basics of stress physiology and biochemistry. This review provides insight into the current information related to the impact of biotic and abiotic factors on variations of various sets of metabolite levels and explores how primary and secondary metabolites help plants in response to these stresses.

Formation and physical characterization of soy protein-isoflavone dispersions and emulsions

Proteins stabilize emulsions by adsorbing at the interface to prevent the natural tendency of droplet coalescence. Polyphenols (plant-derived secondary metabolites) are capable of complexing with proteins through structural interactions. Certain polyphenols have shown influence on interfacial properties of proteins, yet isoflavones specifically have not been widely investigated. Thus, the objective of this research was to study the effect of isoflavones on protein-stabilized oil-in-water emulsions. Soy protein fractions, assessed via SDS-PAGE and bicinchoninic acid assay, contained primarily β-conglycinin (7S) and glycinin (11S). Notable isoflavones identified from HPLC analysis were daidzin, genistin, and glycitin. Physical characteristics (size, zeta potential, polydispersity index, and wettability) of soy protein isolate-isoflavone (SPI–I) dispersions and emulsion droplets were measured with a Zetasizer Nano ZS and goniometer. Isoflavone addition significantly increased the contact angle of sessile drops towards neutral wettability. Heating appeared to significantly improve colloidal stability and emulsion droplets formed with heated SPI-I dispersions sustained size (∼200–245 nm) and zeta potential (∼-30-35 mV) over 7 days, with higher concentrations of isoflavones being generally correlated with smaller emulsion droplets. Collectively, these findings indicate that isoflavone addition improved emulsion stability compared to the control without isoflavones and that they can contribute to colloidal stability of food products.

Comparison of Proanthocyanidin- and Phenolic-Rich Extracts Derived from Pecan Shell and Husk as Elicitors of Induced Resistance Against Phytophthora capsici on Chile Pepper

The use of plant-derived secondary metabolites to induce disease resistance in plants has been well documented. In this study, total phenolics and total proanthocyanidins (PACs) were extracted from the shell and husk of pecan ( Carya illinoinensis) and quantified. Under greenhouse conditions, the extracts were foliarly applied to chile pepper ( Capsicum annuum, cultivar NM 6-4) to compare their ability to induce resistance in plants inoculated with a virulent isolate of Phytophthora capsici. Extractions yielded total phenolic contents of 673 ± 28 and 293 ± 24 mg/g dry weight (DW) for shell and husk and total PAC contents of 1,770.10 ± 158.62 and 901.30 ± 22.84 mg/g DW for shell and husk, respectively. Chile plants treated with total phenolic and PAC extracts from pecan husk or shell or 0.1% salicylic acid, a plant-defense hormone, remained asymptomatic throughout the study for 3 weeks, whereas plants treated with water, which served as a control, died. Both total phenolic and total PAC extracts derived from pecan byproducts can be used within a greenhouse setting as elicitors to induce resistance response in chile pepper against plant pathogens such as P. capsici.

Anti-Obesity Effects of Isorhamnetin and Isorhamnetin Conjugates.

Isorhamnetin is a plant-derived secondary metabolite which belongs to the family of flavonoids. This review summarises the main outcomes described in the literature to date, regarding the effects of isorhamnetin on obesity from in vitro and in vivo studies. The studies carried out in pre-adipocytes show that isorhamnetin is able to reduce adipogenesis at 10 μM or higher doses and that these effects are mediated by Pparγ and by Wnt signalling pathway. Very few studies addressed in rodents are available so far. It seems that treatment periods longer than two weeks are needed by isorhamnetin and its glycosides to be effective as anti-obesity agents. Nevertheless, improvements in glycaemic control can be observed even in short treatments. Regarding the underlying mechanisms of action, although some contradictory results have been found, reductions in de novo lipogenesis and fatty acid uptake could be proposed. Further research is needed to increase the scientific evidence referring to this topic; studies in animal models are essential, as well as randomised clinical trials to determine whether the positive results observed in animals could also be found in humans, in order to determine if isorhamnetin and its glycosides can represent a real tool against obesity.

Protective Effect of Fustin against Huntington's Disease in 3-Nitropropionic Treated Rats via Downregulation of Oxidative Stress and Alteration in Neurotransmitters and Brain-Derived Neurotrophic Factor Activity.

Researchers have revealed that Rhus verniciflua heartwood, which contains fustin as an important component, possesses antioxidant-mediated, anti-mutagenic, and anti-rheumatoid arthritis characteristics. Additionally, out of the numerous plant-derived secondary metabolites, there are various research papers concentrating on flavonoids for potential advantages in neurological illnesses. The current study aims to assess the neuroprotective potential of fustin in rodents over 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD)-like consequences. The efficacy of fustin 50 and 100 mg/kg was studied with multiple-dose administrations of 3-NPA, which experimentally induced HD-like symptoms in rats for 22 days. At the end of the study, several behavioral tests were performed including a beam walk, rotarod, and grip strength tests. Similarly, some biochemical parameters were assessed to support oxidative stress (reduced glutathione-GSH, superoxide dismutase-SOD, catalase-CAT, and malondialdehyde-MDA), alteration in neurotransmitters (gamma-aminobutyric acid-GABA-and glutamate), alteration in brain-derived neurotrophic factor activity, and nitrite levels. Additionally, pro-inflammatory parameters were carried out to evaluate the neuroinflammatory responses associated with streptozotocin such as TNF-α, IL-1β, and COX in the perfused brain. The fustin-treated group exhibited a significant restoration of memory function via modulation in behavioral activities. Moreover, 3-NPA altered biochemical, neurotransmitters, brain protein levels, and neuroinflammatory measures, which fustin efficiently restored. This is the first report demonstrating the efficacy of novel phytoconstituent fustin as a potential future candidate for the treatment of HD via offering neuroprotection by subsiding the oxidative and enzymatic activity in the 3-NPA experimental animal paradigm.

Biotechnology and In Vitro Culture as an Alternative System for Secondary Metabolite Production.

Medicinal plants are rich sources of bioactive compounds widely used as medicaments, food additives, perfumes, and agrochemicals. These secondary compounds are produced under stress conditions to carry out physiological tasks in plants. Secondary metabolites have a complex chemical structure with pharmacological properties. The widespread use of these metabolites in a lot of industrial sectors has raised the need to increase the production of secondary metabolites. Biotechnological methods of cell culture allow the conservation of plants, as well as the improvement of metabolite biosynthesis and the possibility to modify the synthesis pathways. The objective of this review is to outline the applications of different in vitro culture systems with previously reported relevant examples for the optimal production of plant-derived secondary metabolites.

Rosemary essential oil and its components 1,8-cineole and α-pinene induce ROS-dependent lethality and ROS-independent virulence inhibition in Candida albicans.

The essential oil from Rosmarinus officinalis L., a composite mixture of plant-derived secondary metabolites, exhibits antifungal activity against virulent candidal species. Here we report the impact of rosemary oil and two of its components, the monoterpene α-pinene and the monoterpenoid 1,8-cineole, against Candida albicans, which induce ROS-dependent cell death at high concentrations and inhibit hyphal morphogenesis and biofilm formation at lower concentrations. The minimum inhibitory concentrations (100% inhibition) for both rosemary oil and 1,8-cineole were 4500 μg/ml and 3125 μg/ml for α-pinene, with the two components exhibiting partial synergy (FICI = 0.55 ± 0.07). At MIC and 1/2 MIC, rosemary oil and its components induced a generalized cell wall stress response, causing damage to cellular and organelle membranes, along with elevated chitin production and increased cell surface adhesion and elasticity, leading to complete vacuolar segregation, mitochondrial depolarization, elevated reactive oxygen species, microtubule dysfunction, and cell cycle arrest mainly at the G1/S phase, consequently triggering cell death. Interestingly, the same oils at lower fractional MIC (1/8-1/4) inhibited virulence traits, including reduction of mycelium (up to 2-fold) and biofilm (up to 4-fold) formation, through a ROS-independent mechanism.

Biosynthesis Investigations of Terpenoid, Alkaloid, and Flavonoid Antimicrobial Agents Derived from Medicinal Plants.

The overuse of antibiotics in the past decades has led to the emergence of a large number of drug-resistant microorganisms. In recent years, the infection rate caused by multidrug-resistant microorganisms has been increasing, which has become one of the most challenging problems in modern medicine. Plant-derived secondary metabolites and their derivatives have been identified to display significant antimicrobial abilities with good tolerance and less adverse side effects, potentially having different action mechanisms with antibiotics of microbial origin. Thus, these phyto-antimicrobials have a good prospect in the treatment of multidrug-resistant microorganisms. Terpenoids, alkaloids, and flavonoids made up the predominant part of the currently reported phytochemicals with antimicrobial activities. Synthetic biology research around these compounds is one of the hotspot fields in recent years, which not only has illuminated the biosynthesis pathways of these phyto-antimicrobials but has also offered new methods for their production. In this review, we discuss the biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents—using artemisinin and oleanolic acid (terpenoids), berberine and colchicine (alkaloids), and baicalin (flavonoids) as examples—around their antimicrobial action mechanisms, biosynthesis pathway elucidation, key enzyme identification, and heterologous production, in order to provide useful hints for plant-derived antimicrobial agent discovery and development.

Investigation of Selected Medicinal Plants for Their Anti-Obesity Properties.

Obesity, which is a risk factor for diabetes, hypertension, cardiovascular diseases, and cancer, is caused serious health problems and economic costs on a global scale. Nowadays, pancreatic lipase inhibitors that cause inhibition of lipid digestion and lipid absorption are one of the limited treatment approaches for obesity. Plant-derived secondary metabolites can be used for treating obesity. The aim of this study was to research the antiobesity potential of Amaranthus albus L. (Amaranthaceae), Helichrysum compactum Boiss. (Asteraceae), Chenopodium album L. (Chenopodiaceae), and Agrimonia eupatoria L. (Rosaceae). To detect the antiobesity potentials of the plants, in vitro lipase inhibitory activity studies by spectroscopic method and quantitative analysis studies of some anti-obesity effective secondary metabolites by reversed-phase high performance liquid chromatography (RP-HPLC) technique were carried out. In vitro lipase inhibitory studies showed that all plant extracts possess lipase inhibitory effect, and the highest lipase inhibitory potential was observed for H. compactum (IC50: 45.70 μg/mL ± 2.3618). According to HPLC analyses, p-coumaric acid (0.27 mg/g) in A. albus; benzoic acid (0.33 mg/g) in C. album; vanillic acid (7.32 mg/g), syringaldehyde (14.97 mg/g), quercetin (4.66 mg/g), p-coumaric acid (0.71 mg/g), and benzoic acid (3.43 mg/g) in H. compactum; p-coumaric acid (0.71 mg/g) and benzoic acid (3.43 mg/g) in A. eupatoria were detected. In conclusion, H. compactum is the most remarkable natural source for the study. The fact remains that all plants may be promising candidates for treating obesity.

Jasmonates in plant growth and development and elicitation of secondary metabolites: An updated overview.

Secondary metabolites are incontestably key specialized molecules with proven health-promoting effects on human beings. Naturally synthesized secondary metabolites are considered an important source of pharmaceuticals, food additives, cosmetics, flavors, etc., Therefore, enhancing the biosynthesis of these relevant metabolites by maintaining natural authenticity is getting more attention. The application of exogenous jasmonates (JAs) is well recognized for its ability to trigger plant growth and development. JAs have a large spectrum of action that covers seed germination, hypocotyl growth regulation, root elongation, petal expansion, and apical hook growth. This hormone is considered as one of the key regulators of the plant’s growth and development when the plant is under biotic or abiotic stress. The JAs regulate signal transduction through cross-talking with other genes in plants and thereby deploy an appropriate metabolism in the normal or stressed conditions. It has also been found to be an effective chemical elicitor for the synthesis of naturally occurring secondary metabolites. This review discusses the significance of JAs in the growth and development of plants and the successful outcomes of jasmonate-driven elicitation of secondary metabolites including flavonoids, anthraquinones, anthocyanin, xanthonoid, and more from various plant species. However, as the enhancement of these metabolites is essentially measured via in vitro cell culture or foliar spray, the large-scale production is significantly limited. Recent advancements in the plant cell culture technology lay the possibilities for the large-scale manufacturing of plant-derived secondary metabolites. With the insights about the genetic background of the metabolite biosynthetic pathway, synthetic biology also appears to be a potential avenue for accelerating their production. This review, therefore, also discussed the potential manoeuvres that can be deployed to synthesis plant secondary metabolites at the large-scale using plant cell, tissue, and organ cultures.

Effects of Plant Metabolites on the Growth of COVID-19 (Coronavirus Disease-19) Including Omicron Strain.

According to recent reports out of India, a new strain of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) B1.1.529 Omicron virus has emerged. In comparison to the Wuhan (WHU) strain and the delta variant, this variant showed a far stronger effect on the angiotensin converting enzyme2 (ACE2) receptor. There are several medicinal compounds in plant metabolites, and their diverse chemical structures make them ideal for the treatment of serious illnesses. It's possible that some of these could be useful alternative pharmaceuticals, as well as a starting point for the repurposing of existing medications and new chemical discoveries. SARS-CoV-2 infection triggered a worldwide epidemic of the severe acute respiratory syndrome (SARS). There have been trials for different therapies for SARS-CoV-2 and so also there are recent announcements of extensive research into the development of viable medicines for this global health calamity. After a thorough examination of plant-derived treatments for COVID-19, investigators in the current study decided to focus on plant-derived secondary metabolites (PSMs). According to some researchers, new MDR (Multi-Drug Resistant) antibiotics may one day be developed due to the adaptability of secondary metabolites. Identifying plant metabolites that can treat a wide range of viral infections was one of the study's aims. Many natural medications that could be recommended for the treatment of COVID-19 were discovered as a result of this research, including remedies from plant families, viral candidates that are susceptible, antiviral assays, and mechanisms of therapeutic action. The findings of this study will inspire further research and speed up the development of new antiviral plant-based medications.

RETRACTED: The potential of plant-derived secondary metabolites as novel drug candidates against Klebsiella pneumoniae: Molecular docking and simulation investigation

Klebsiella pneumoniae is an important multidrug-resistant pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. The pathogenesis of this microbe is caused by several key proteins; one of them is type 3 fimbrial proteins, which has been known for its crucial role in the host cell invasion. Therefore, targeting fimbriae protein can be a solution for treating this pathogenic disease. Plant Secondary metabolites with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for plant secondary metabolites at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we have employed plant derived secondary metabolites to predict new drug targets of type 3 fimbrial protein of K. pneumoniae. Subsequently, structure-based virtual screening was performed to identify compounds showing the best binding confirmation with the target enzyme and forming a stable complex. Molecular dynamics simulations of the protein-ligand complex indicated that the intermolecular hydrogen bonds formed between the protein and ligand complex remain stable during the simulation time. The interaction shown by the compounds provides an important insight into the mechanism involved in the ligand-receptor interaction. The model will aid in the development of a drug with improved efficacy and reduced side effects. Thus, vernolide could serve as a drug for treating pneumonia infections in humans. The drug likeliness prediction on this derivative also supports its suitability as a drug candidate. However, an in vitro and in vivo analysis of the selected compound is necessary for further validation before administration of the drug to human beings.

VNN model cross validation towards Accuracy, Sensitivity, Specificity and kappa performance measures of β-caryophyllene using a restricted-unrestricted applicability domain on Artificial Intelligence & Machine Learning approach based in-silico prediction

Wide-reaching interest in use of plant derived secondary metabolites (PDSMs) has been growing world over. This implies that the beneficial effects of plant based natural products (PBNPs) being rediscovered and harnessed for the development of novel drugs; drug-leads and structural background for drug design. Survey of literature on the indigenous use of traditional medicinal knowledge bestows ethnopharmacological potentials of PBNPs that has inspired drug design and development through research in drug discovery; PBNPs provide baseline for the development of drug leads against various pharmacological targets. Studies indicate that Cymbopogon martini Essential Oil (CMEO) exhibits a wide range of biological activities (anticancer, antidiabetic, antibacterial, antifungal, antioxidant, hepatoprotective and insecticide) attributed to the presence of bio-active secondary metabolites (BASM). However, wide-spread application of CMEO is limited because of typical odor, color and taste. In the present study, In-silico Absorption, Distribution, Metabolism, Elimination, Toxicity (ADMET) studies of β-caryophyllene (BCP) from Cymbopogon martinii is envisaged. β-caryophyllene enhances wound healing through multiple routes therefore, Non AMES toxic, Non-carcinogens, and biodegradable nature of β-caryophyllene prospects this compound as considered as an apt lead for the development of drugs for the treatment of cuts and wounds besides other diseases viz., diabetics, cancer, metabolic inflammation and other long term complications associated with these diseases. In particular, BCP inhibits cytochrome P450 isoforms (CYP3A4) that metabolize xenobiotics and results in adverse effects. Pharmacokinetic properties and predicted score values of β-caryophyllene have highlighted that both pharmacological and toxicological aspects need to be further investigated before put to clinical trials.
 Keywords: ADMET; β-caryophyllene; Cymbopogon martinii; Cardiotoxicity; Cytotoxicity; Drugability; Pharmacokinetics; Bioactivity; Essential Oil;

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury.

Despite the progression in targeting the complex pathophysiological mechanisms of neurodegenerative diseases (NDDs) and spinal cord injury (SCI), there is a lack of effective treatments. Moreover, conventional therapies suffer from associated side effects and low efficacy, raising the need for finding potential alternative therapies. In this regard, a comprehensive review was done regarding revealing the main neurological dysregulated pathways and providing alternative therapeutic agents following SCI. From the mechanistic point, oxidative stress and inflammatory pathways are major upstream orchestras of cross-linked dysregulated pathways (e.g., apoptosis, autophagy, and extrinsic mechanisms) following SCI. It urges the need for developing multitarget therapies against SCI complications. Polyphenols, as plant-derived secondary metabolites, have the potential of being introduced as alternative therapeutic agents to pave the way for treating SCI. Such secondary metabolites presented modulatory effects on neuronal oxidative stress, neuroinflammatory, and extrinsic axonal dysregulated pathways in the onset and progression of SCI. In the present review, the potential role of phenolic compounds as critical phytochemicals has also been revealed in regulating upstream dysregulated oxidative stress/inflammatory signaling mediators and extrinsic mechanisms of axonal regeneration after SCI in preclinical and clinical studies. Additionally, the coadministration of polyphenols and stem cells has shown a promising strategy for improving post-SCI complications.

Engineering Considerations to Produce Bioactive Compounds from Plant Cell Suspension Culture in Bioreactors.

The large-scale production of plant-derived secondary metabolites (PDSM) in bioreactors to meet the increasing demand for bioactive compounds for the treatment and prevention of degenerative diseases is nowadays considered an engineering challenge due to the large number of operational factors that need to be considered during their design and scale-up. The plant cell suspension culture (CSC) has presented numerous benefits over other technologies, such as the conventional whole-plant extraction, not only for avoiding the overexploitation of plant species, but also for achieving better yields and having excellent scaling-up attributes. The selection of the bioreactor configuration depends on intrinsic cell culture properties and engineering considerations related to the effect of operating conditions on thermodynamics, kinetics, and transport phenomena, which together are essential for accomplishing the large-scale production of PDSM. To this end, this review, firstly, provides a comprehensive appraisement of PDSM, essentially those with demonstrated importance and utilization in pharmaceutical industries. Then, special attention is given to PDSM obtained out of CSC. Finally, engineering aspects related to the bioreactor configuration for CSC stating the effect of the operating conditions on kinetics and transport phenomena and, hence, on the cell viability and production of PDSM are presented accordingly. The engineering analysis of the reviewed bioreactor configurations for CSC will pave the way for future research focused on their scaling up, to produce high value-added PDSM.

Potential Anti-Mycobacterium tuberculosis Activity of Plant Secondary Metabolites: Insight with Molecular Docking Interactions.

Tuberculosis (TB) is a recurrent and progressive disease, with high mortality rates worldwide. The drug-resistance phenomenon of Mycobacterium tuberculosis is a major obstruction of allelopathy treatment. An adverse side effect of allelopathic treatment is that it causes serious health complications. The search for suitable alternatives of conventional regimens is needed, i.e., by considering medicinal plant secondary metabolites to explore anti-TB drugs, targeting the action site of M. tuberculosis. Nowadays, plant-derived secondary metabolites are widely known for their beneficial uses, i.e., as antioxidants, antimicrobial agents, and in the treatment of a wide range of chronic human diseases (e.g., tuberculosis), and are known to “thwart” disease virulence. In this regard, in silico studies can reveal the inhibitory potential of plant-derived secondary metabolites against Mycobacterium at the very early stage of infection. Computational approaches based on different algorithms could play a significant role in screening plant metabolites against disease virulence of tuberculosis for drug designing.

Targeting Mitochondria by Plant Secondary Metabolites: A Promising Strategy in Combating Parkinson's Disease.

Parkinson’s disease (PD) is one of the most prevalent and debilitating neurodegenerative conditions, and is currently on the rise. Several dysregulated pathways are behind the pathogenesis of PD; however, the critical targets remain unclear. Accordingly, there is an urgent need to reveal the key dysregulated pathways in PD. Prevailing reports have highlighted the importance of mitochondrial and cross-talked mediators in neurological disorders, genetic changes, and related complications of PD. Multiple pathophysiological mechanisms of PD, as well as the low efficacy and side effects of conventional neuroprotective therapies, drive the need for finding novel alternative agents. Recently, much attention has been paid to using plant secondary metabolites (e.g., flavonoids/phenolic compounds, alkaloids, and terpenoids) in the modulation of PD-associated manifestations by targeting mitochondria. In this line, plant secondary metabolites have shown promising potential for the simultaneous modulation of mitochondrial apoptosis and reactive oxygen species. This review aimed to address mitochondria and multiple dysregulated pathways in PD by plant-derived secondary metabolites.

GCMS Profile of Bioactive Compounds with Therapeutic Potential in Beta vulgaris (L.) Ethanolic Leaf Extracts

Plants, animals, and microorganisms have all been shown to have health benefits for humans. According to World Health Organization, plant medicines continue to be used by 80 percent of the world’s population in developing countries. Plant-derived secondary metabolites are macromolecules that are biosynthesized in plants and have a variety of biological properties that are beneficial to humans, including antiallergic, anti-inflammatory, anti-diabetic, and antioxidant properties. Therefore, the present investigation was done to determine the bioactive compounds present in Beta vulgaris (L.) leaves powder using Perkin-Elmer Gas Chromatography-Mass Spectrometry, while the mass spectra of the compounds found in the extract matched the National Institute of Standards and Technology (NIST) library. GC-MS analysis of an ethanolic extract of Beta vulgaris (L.) revealed the presence of 25 bioactive compounds with different area percentages and structural details. The major bioactive compounds are 1,3,5,7- Tetroxane (73.1%), Decane (83.1%), Azulene (73.8%), 4-Hepten-2-one, 5-ethyl-3,3,4-trimethyl-(71.1%), 6-Amino-1,3,5-triazine-2,4 (1H, 3H)-dione(65.1%), Phthalic acid, 4-bromophenyl ethyl ester(83.7%), Neophtadiene(93.1%), Neophytadiene (88.2%)Hexadecanoic acid, methyl ester(84.8%), n-Hexadecanoic acid(84.3%), Phytol(86.0%), 9- octadecenoic acid, (E)(88.6%), 2-Hexadecen-1-ol,3,7,11,15-tetramethyl-acetate,[R-[R*,R*-(E)]]-(64.0%), 1-Tricosene(72.3%) and 17-Pentatriacontene(65.6%). Most identified compounds have bioactivities such as Antimalaria, Anti-inflammatory, Antibacterial, Antifungal, Antiviral, Antidiabetic, Antioxidant, Anticancer, Analgesic, Anti-hyperlipidemic, Hypocholesterolemic, Hepatoprotective, and Anti-androgenic, so that they can be recommended as a plant of phytopharmaceutical importance. Therefore ethanol extract of Beta vulgaris (L.) leaves proves as a potential source of bioactive compounds of pharmacological importance.