Natural Secondary Metabolites Research Articles

Biotechnological production of ectoine: current status and prospects.

Ectoine is an important natural secondary metabolite in halophilic microorganisms. It protects cells against environmental stressors, such as salinity, freezing, drying, and high temperatures. Ectoine is widely used in medical, cosmetic, and other industries. Due to the commercial market demand of ectoine, halophilic microorganisms are the primary method for producing ectoine, which is produced using the industrial fermentation process "bacterial milking." The method has some limitations, such as the high salt concentration fermentation, which is highly corrosive to the equipment, and this also increases the difficulty of downstream purification and causes high production costs. The ectoine synthesis gene cluster has been successfully heterologously expressed in industrial microorganisms, and the yield of ectoine was significantly increased and the cost was reduced. This review aims to summarize and update microbial production of ectoine using different microorganisms, environments, and metabolic engineering and fermentation strategies and provides important reference for the development and application of ectoine.

Research Advances in Clinical Applications, Anticancer Mechanism, Total Chemical Synthesis, Semi-Synthesis and Biosynthesis of Paclitaxel.

Paclitaxel, a natural secondary metabolite isolated and purified from the bark of the Taxus tree, is considered one of the most successful natural anticancer drugs due to its low toxicity, high potency and broad-spectrum anticancer activity. Taxus trees are scarce and slow-growing, and with extremely low paclitaxel content, the contradiction between supply and demand in the market is becoming more and more intense. Therefore, researchers have tried to obtain paclitaxel by various methods such as chemical synthesis, artificial culture, microbial fermentation and tissue cell culture to meet the clinical demand for this drug. This paper provides a comprehensive overview of paclitaxel extraction, combination therapy, total synthesis, semi-synthesis and biosynthesis in recent years and provides an outlook, aiming to provide a theoretical basis and reference for further research on the production and application of paclitaxel in the future.

The Interplay of Genital Herpes with Cellular Processes: A Pathogenesis and Therapeutic Perspective.

Genital herpes, primarily caused by herpes simplex virus-2 (HSV-2), remains a pressing global health concern. Its remarkable ability to intertwine with cellular processes, from harnessing host machinery for replication to subverting antiviral defenses like autophagy and programmed cell death, exemplifies the intricate interplay at the heart of its pathogenesis. While the biomedical community has extensively researched antiviral interventions, the efficiency of these strategies in managing HSV-2 remains suboptimal. Recognizing this, attention has shifted toward leveraging host cellular components to regulate HSV-2 replication and influence the cell cycle. Furthermore, innovative interventional strategies-including drug repurposing, microbivacs, connecting the host microbiome, and exploiting natural secondary metabolites-are emerging as potential game changers. This review summarizes the key steps in HSV-2 pathogenesis and newly discovered cellular interactions, presenting the latest developments in the field, highlighting existing challenges, and offering a fresh perspective on HSV-2's pathogenesis and the potential avenues for its treatment by targeting cellular proteins and pathways.

Modulation of hypoxia-inducible factor-1 signaling pathways in cancer angiogenesis, invasion, and metastasis by natural compounds: a comprehensive and critical review.

Tumor cells employ multiple signaling mediators to escape the hypoxic condition and trigger angiogenesis and metastasis. As a critical orchestrate of tumorigenic conditions, hypoxia-inducible factor-1 (HIF-1) is responsible for stimulating several target genes and dysregulated pathways in tumor invasion and migration. Therefore, targeting HIF-1 pathway and cross-talked mediators seems to be a novel strategy in cancer prevention and treatment. In recent decades, tremendous efforts have been made to develop multi-targeted therapies to modulate several dysregulated pathways in cancer angiogenesis, invasion, and metastasis. In this line, natural compounds have shown a bright future in combating angiogenic and metastatic conditions. Among the natural secondary metabolites, we have evaluated the critical potential of phenolic compounds, terpenes/terpenoids, alkaloids, sulfur compounds, marine- and microbe-derived agents in the attenuation of HIF-1, and interconnected pathways in fighting tumor-associated angiogenesis and invasion. This is the first comprehensive review on natural constituents as potential regulators of HIF-1 and interconnected pathways against cancer angiogenesis and metastasis. This review aims to reshape the previous strategies in cancer prevention and treatment.

A Multi-Label Learning Framework for Predicting Chemical Classes and Biological Activities of Natural Products from Biosynthetic Gene Clusters.

Natural products (NP) or secondary metabolites, as a class of small chemical molecules that are naturally synthesized by chromosomally clustered biosynthesis genes (also called biosynthetic gene clusters, BGCs) encoded enzymes or enzyme complexes, mediates the bioecological interactions between host and microbiota and provides a natural reservoir for screening drug-like therapeutic pharmaceuticals. In this work, we propose a multi-label learning framework to functionally annotate natural products or secondary metabolites solely from their catalytical biosynthetic gene clusters without experimentally conducting NP structural resolutions. All chemical classes and bioactivities constitute the label space, and the sequence domains of biosynthetic gene clusters that catalyse the biosynthesis of natural products constitute the feature space. In this multi-label learning framework, a joint representation of features (BGCs domains) and labels (natural products annotations) is efficiently learnt in an integral and low-dimensional space to accurately define the inter-class boundaries and scale to the learning problem of many imbalanced labels. Computational results on experimental data show that the proposed framework achieves satisfactory multi-label learning performance, and the learnt patterns of BGCs domains are transferrable across bacteria, or even across kingdom, for instance, from bacteria to Arabidopsis thaliana. Lastly, take Arabidopsis thaliana and its rhizosphere microbiome for example, we propose a pipeline combining existing BGCs identification tools and this proposed framework to find and functionally annotate novel natural products for downstream bioecological studies in terms of plant-microbiota-soil interactions and plant environmental adaption.

An Outlook on Pathological Pathways of Diabetes and Molecular Mechanisms of Anti-diabetic Phytobioactives

Background & Purpose: Diabetes is a disease that has affected many people worldwide. According to the World Health Organization, approximately 80% of humans still rely on conventional or folk medicament in developed countries. The effectiveness of herbal medicines was credited to the phytochemical components. Objective: This review aims to highlight the pathological pathways of diabetes and the antidiabetic mechanism of phytochemicals. Materials and Methods: This organized search was compiled from the databases such as PubMed, Scopus, Embase, ScienceDirect, Web of Science, and Google Scholar till February 2023. Results: Inflammatory and oxidative stress are mainly two examples of pathological pathways of diabetes that are explored. The reported antidiabetic phytochemicals work by increasing insulin secretion, lowering hepatic glucose output, controlling specific enzymes, and utilizing other mechanisms. For instance, studies on α-glucosidase inhibitors, modulation peroxisome proliferator-activated receptor-α, hypolipidaemic activity, antioxidants, inhibition of glycolytic enzymes like phosphoenolpyruvate carboxykinase, improvement of glycosylated haemoglobin and increased expression of glucose transporters have been conducted. Conclusion: Many natural secondary metabolites (phytochemicals) have significant potential for the manufacture of marketable, new, and efficient anti-diabetic medicines which can be used for clinical purposes.

Screening of Antiviral Efficacy of Few Seaweeds of Tamil Nadu Coast

Lately there has been a lot of interest worldwide in studies on the antiviral activities of marine natural secondary metabolites, notably marine polysaccharides. It has been established that polysaccharides made from marine sources and their derivatives have antiviral effects against potent viruses. Agricultural, biological, food, and pharmaceutical industries all make extensive use of goods obtained from algae. The most well-known chemical components found in algae are polysaccharides, which have been the subject of a variety of studies because of their varied bioactivities. Polysaccharides made from algae have recently risen to the top of pharmaceutical research due to their fascinating antiviral potential. Currently, COVID-19 can be prevented with vaccination, but the brown alga Sargassum wightii has several bioactive compounds that have the following qualities and may be a better option. S. wightii is one of the marine algae species that is rich in sulfated polysaccharides, the secondary metabolites which have antiviral action and the capacity to prevent viral proliferation. Fucoidan, a long-chain sulfated polysaccharide found in various brown algae, has potent antiviral effects. Additionally, sulfated polysaccharides from green algae (such as ulvans) and red algae (such as carrageenan), and lectins from red algae (such as griffithsin) have antiviral therapeutic agents against coronaviruses and other viruses. This research focuses on screening seaweeds for possible antiviral compounds to treat viral infections notably COVID-19.

Cryopreservation of bioflavonoid-rich plant sources and bioflavonoid-microcapsules: emerging technologies for preserving bioactivity and enhancing nutraceutical applications.

Bioflavonoids are natural polyphenolic secondary metabolites that are medicinal. These compounds possess antitumor, cardioprotective, anti-inflammatory, antimicrobial, antiviral, and anti-psoriasis properties to mention a few. Plant species that contain bioflavonoids should be preserved as such. Also, the bioactivity of the bioflavonoids as neutraceutical compounds is compromised following extraction due to their sensitivity to environmental factors like light, pH, and temperature. In other words, the bioflavonoids' shelf-life is affected. Scientists noticed that bioflavonoids have low solubility properties, poor absorption, and low bioavailability following consumption. Researchers came up with methods to encapsulate bioflavonoids in order to circumvent the challenges above and also to mask the unpleasant order these chemicals may have. Besides, scientists cryopreserve plant species that contain bioflavonoids. In this review, we discuss cryopreservation and bioflavonoid microencapsulation focusing mainly on vitrification, slow freezing, and freeze-drying microencapsulation techniques. In addition, we highlight bioflavonoid extraction techniques, medicinal properties, challenges, and future perspectives of cryopreservation and microencapsulation of bioflavonoids. Regardless of the uniqueness of cryopreservation and microencapsulation as methods to preserve bioflavonoid sources and bioflavonoids' bioactivity, there are challenges reported. Freeze-drying technology is costly. Cryoprotectants damage the integrity of plant cells, to say the least. Researchers are working very hard to overcome these challenges. Encapsulating bioflavonoids via coaxial electrospray and then cryopreserving the micro/nanocapsules produced can be very interesting.

T-2 toxin induces cardiotoxicity by activating ferroptosis and inhibiting heme oxygenase-1

T-2 toxin, a natural secondary sesquiterpenoid metabolite produced by numerous strains of Fusarium fungi, is prevalent in both contaminated food and the environment. T-2 toxin is known to be highly toxic to the cardiovascular system, but the precise mechanisms that lead to T-2 toxin-induced cardiotoxicity are not yet fully understood. Recent findings indicate that ferroptosis is a pivotal factor in cardiovascular damage and exhibits a strong correlation with the detrimental impacts of T-2 toxin. The present study was designed to examine the involvement of ferroptosis in T-2 toxin-induced cardiac injury. Male mice and human cardiomyocytes were subjected to T-2 toxin for 24 h to induce acute cardiotoxicity for in vivo and in vitro studies, respectively. Our results demonstrated that T-2 toxin increased reactive oxygen species production, malondialdehyde, and decreased glutathione/oxidized glutathione and adenosine triphosphate levels. Furthermore, T-2 toxin was observed to activate ferroptosis, as evidenced by an increase in iron (Fe2+) concentration and upregulation of prostaglandin endoperoxide synthase 2, downregulation of glutathione peroxidase 4 and ferritin heavy chain 1, as well as ferroptotic morphological alterations. Inhibition of ferroptosis by Liproxstatin-1 reversed T-2 toxin-induced cardiac injury. Additionally, the downregulation of heme oxgenase-1 (HO-1) expression by T-2 toxin exacerbates ferroptosis and oxidative damage, which can be further aggravated by HO-1 inhibition with Sn-protoporphyrin. These findings provide novel insights into the mechanism of T-2 toxin-induced cardiotoxicity and suggest that targeting ferroptosis and HO-1 may represent a promising cardioprotective strategy against T-2 toxin.

Impacts of Plant-derived Secondary Metabolites for Improving Flora in Type 2 Diabetes.

Diabetes has become a problem that plagues public healthcare systems. Recent studies have shown that intestinal flora exerts positive therapeutic effects on metabolic diseases, and plant-derived secondary metabolites are safe, effective and easy to prepare and also have an impact on intestinal flora and diabetes; these drugs have rarely been reviewed before as a class of drugs for diabetes, especially focusing on the intestinal flora. Therefore, studying the relationship between plant-derived secondary metabolites and diabetes mellitus is crucial. The objective of this study is to summarize and investigate the therapeutic mechanism of drugs extracted from natural plants effects on type 2 diabetes mellitus. The relationship between flora and type 2 diabetes was investigated by reviewing the recent experimental literature, and the pathways available for natural plant-derived secondary metabolites in the treatment of type 2 diabetes were summarized. The therapeutic mechanisms of common plant-derived secondary metabolites for type 2 diabetes were summarized with a focus on the prebiotic efficacy of natural plant-derived secondary metabolites and the modulation of intestinal flora, and the mechanisms through which plantderived secondary metabolites treat type 2 diabetes via effects on intestinal flora are further reviewed. Common plant-derived secondary metabolites can play a role in regulating bacteria in the intestinal tract by enriching beneficial bacteria and removing harmful bacteria to achieve their therapeutic effect on type 2 diabetes. In addition, due to their excellent ability to regulate intestinal flora, plant-derived secondary metabolites may also have excellent efficacy in cancer and obesity, among other diseases.

Saikosaponin D exerts cytotoxicity on human endometrial cancer ishikawa cells by inducing apoptosis and inhibiting metastasis through MAPK pathways.

Saikosaponin D (SSD) is one of plant secondary metabolic active substance with effective anti-tumor ability; however, the toxicity of Saikosaponin D on human endometrial cancer Ishikawa cells is still unclear. Our results revealed that SSD displayed cytotoxicity on the Ishikawa cell with an IC50 = 15.69 μM, but was non-toxic to the human normal cell line HEK293. SSD could upregulate p21 and Cyclin B to keep cells in the G2/M stage. In addition, it activated the death receptor and mitochondrion routes to induce apoptosis in Ishikawa cells. The transwell chamber and wound healing results showed that SSD inhibited the cell migration and invasion. In addition, we found that it was closely related to the MAPK cascade pathway, and it could mediate the three classical MAPK pathways to block cell metastasis. In conclusion, SSD could be potentially beneficial as a natural secondary metabolite in preventing and treating endometrial carcinoma.

Synthetic Study of Natural Metabolites Containing a Benzo[c]oxepine Skeleton: Heterocornol C and D.

A versatile strategy for the enantioselective synthesis of a benzo[c]oxepine structural core containing natural secondary metabolites was developed. The key steps of the synthetic approach include ring-closing alkene metathesis for seven-member ring construction, the Suzuki-Miyaura cross-coupling reaction for the installation of the double bond and Katsuki-Sharpless asymmetric epoxidation for the introduction of chiral centers. The first total synthesis and absolute configuration assignment of heterocornol D (3a) were achieved. Four stereoisomers, 3a, ent-3a, 3b and ent-3b, of this natural polyketide were prepared, starting with 2,6-dihydroxy benzoic acid and divinyl carbinol. The absolute and relative configuration of heterocornol D was assigned via single-crystal X-ray analysis. The extension of the described synthetic approach is further presented with the synthesis of heterocornol C by applying the ether group reduction method to the lactone.

Peniciriols A and B, two new citrinin derivatives from an endophytic fungus Penicillum citrinum TJNZ-27

Two undescribed citrinin derivatives, named peniciriols A-B (1–2), together with six known compounds were isolated from endophytic fungus Penicillum citrinum TJNZ-27. The structures of two new compounds were well established by the detail interpretation of NMR and HRESIMS data as well as ECD measurement powered by molecular calculation. Among them, compound 1 shared an unprecedented dimerized citrinin skeleton with the formation of an intriguing 9H-xanthene ring system, whereas compound 2 possess a highly substituted phenylacetic acid skeleton, which was rarely-occurring in natural secondary metabolites. Moreover, these novel compounds were tested for cytotoxic and antibacterial activities, whereas these novel compounds did not exhibit any noticeable cytotoxic or antibacterial activities.

Tyrosol induces multiple drug resistance in yeast Saccharomyces cerevisiae.

In yeast, multiple (pleiotropic) drug resistance (MDR) transporters efflux xenobiotics from the cytoplasm to the environment. Additionally, upon the accumulation of xenobiotics in the cells, MDR genes are induced. At the same time, fungal cells can produce secondary metabolites with physico-chemical properties similar to MDR transporter substrates. Nitrogen limitation in yeast Saccharomyces cerevisiae leads to the accumulation of phenylethanol, tryptophol, and tyrosol, which are products of aromatic amino acid catabolism. In this study, we investigated whether these compounds could induce or inhibit MDR in yeast. Double deletion of PDR1 and PDR3 genes, which are transcription factors that upregulate the expression of PDR genes, reduced yeast resistance to high concentrations of tyrosol (4-6 g/L) but not to the other two tested aromatic alcohols. PDR5 gene, but not other tested MDR transporter genes (SNQ2, YOR1, PDR10, PDR15) contributed to yeast resistance to tyrosol. Tyrosol inhibited the efflux of rhodamine 6G (R6G), a substrate for MDR transporters. However, preincubating yeast cells with tyrosol induced MDR, as evidenced by increased Pdr5-GFP levels and reduced yeast ability to accumulate Nile red, another fluorescent MDR-transporter substrate. Moreover, tyrosol inhibited the cytostatic effect of clotrimazole, the azole antifungal. Our results demonstrate that a natural secondary metabolite can modulate yeast MDR. We speculate that intermediates of aromatic amino acid metabolites coordinate cell metabolism and defense mechanisms against xenobiotics.

Nematostatic activity of isoprenylated guanidine alkaloids from Pterogyne nitens and their interaction with acetylcholinesterase

Although new nematicides have appeared, the demand for new products less toxic and more efficient for the control of plant-parasitic nematodes are still high. Consequently, studies on natural secondary metabolites from plants, to develop new nematicides, have increased. In this work, nineteen extracts from eleven Brazilian plant species were screened for activity against Meloidogyne incognita. Among them, the extracts of Piterogyne nitens showed a potent nematostatic activity. The alkaloid fraction obtained from the ethanol extract of leaves of P. nitens was more active than the coming extract. Due to the promising activity from the alkaloid fraction, three isoprenylated guanidine alkaloids isolated from this fraction, galegine (1), pterogynidine (2), and pterogynine (3) were tested, showing similar activity to the alkaloid fraction, which was comparable to that of the positive control Temik at 250 μg/mL. At lower concentrations (125−50 μg/mL), compound 2 showed to be the most active one. As several nematicides act through inhibition of acetylcholinesterase (AChE), the guanidine alkaloids were also employed in two in vitro AChE assays. In both cases, compound 2 was more active than compounds 1 and 3. Its activity was considered moderated compared to the control (physostigmine). Compound 2 was selected for an in silico study with the electric eel (Electrophorus electricus) AChE, showing to bind mostly to the same site of physostigmine in the AChEs, pointing out that this could be the mechanism of action for this compound. These results suggested that the guanidine alkaloids 1,2 and 3 from P. nitens are promising for the development of new products to control M. incognita, especially guanidine 2, and encourage new investigations to confirm the mechanism of action, as well as to determine the structure-activity relationship of the guanidine alkaloids.

Integrating in Silico and In Vitro Studies to Screen Anti-Staphylococcus aureus Activity From Vietnamese Ganoderma multiplicatum and Ganoderma sinense

Background: Staphylococcus aureus is a nosocomial pathogen responsible for many serious infectious diseases in humans. Finding the anti- S. aureus agents is a time-consuming and costly process. Recently, computational methods have provided a better understanding of the interactions between herbal medicine drug targets to help clinical practitioners rationally design herbal formulae. Methods: In this study, molecular docking simulation was applied to screen a list of natural secondary metabolites from Ganoderma sp. on the protein target S. aureus sortase A. Molecular dynamics models were used to assess the stability of protein–ligand complexes during the first 100 ns. To validate the computational results, 2 Ganoderma species, G. multiplicatum VNKKK1901 and G. sinense VNKKK1902, were tested for antibacterial activity against S. aureus using the disk diffusion method. Results: The results showed that, among the selected compounds, ganosinensin B and ganosinoside A generated the highest binding energy on S. aureus sortase A, and demonstrated strong and stable binding capacity to proteins. In addition, the extracts of G. sinense VNKKK1902 and G. multiplicatum VNKKK1901 were bactericidal, with minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) ratios of 2. Conclusion: Our findings provide the first scientific report on the antibacterial activity of Ganoderma sp., which contain 2 promising compounds, ganosinensin B and ganosinoside A, as potential hits for developing novel drugs capable of supporting treatment of S. aureus infection.

Application of Data Modeling, Instrument Engineering and Nanomaterials in Selected Medid the Scientific Recinal Plant Tissue Culture

At present, most precious compounds are still obtained by plant cultivation such as ginsenosides, glycyrrhizic acid, and paclitaxel, which cannot be easily obtained by artificial synthesis. Plant tissue culture technology is the most commonly used biotechnology tool, which can be used for a variety of studies such as the production of natural compounds, functional gene research, plant micropropagation, plant breeding, and crop improvement. Tissue culture material is a basic and important part of this issue. The formation of different plant tissues and natural products is affected by growth conditions and endogenous substances. The accumulation of secondary metabolites are affected by plant tissue type, culture method, and environmental stress. Multi-domain technologies are developing rapidly, and they have made outstanding contributions to the application of plant tissue culture. The modes of action have their own characteristics, covering the whole process of plant tissue from the induction, culture, and production of natural secondary metabolites. This paper reviews the induction mechanism of different plant tissues and the application of multi-domain technologies such as artificial intelligence, biosensors, bioreactors, multi-omics monitoring, and nanomaterials in plant tissue culture and the production of secondary metabolites. This will help to improve the tissue culture technology of medicinal plants and increase the availability and the yield of natural metabolites.

Chemometric-guided chemical marker selection: A case study of the heat-clearing herb Scrophularia ningpoensis.

The selection of medicinal plants' chemical markers focuses on bioactivity as the primary goal, followed by the nature of secondary metabolites, their stability, and availability. However, herbal medicines are valued for their complex and holistic pharmacological effects. A correct chemical marker can be carefully selected by a systematic clarification of their chemical-biological relationships. In the current study, the multi-informative molecular networking (MIMN) approach was employed to construct the anti-inflammatory metabolomic pattern of a heat-clearing herb, Scrophularia ningpoensis Hemsl. (S. ningpoensis). The MIMN molecular families characterized by cinnamic acid glycosides showed a higher bioactivity score compared with the other two major chemical classes (iridoid glycosides and iridoid-cinnamic acid glycosides). The Global Natural Product Social Molecular Networking (GNPS) and Reaxys database were used to assist in the putative annotation of eighteen metabolites from the bioactive and non-bioactive molecular families. The anti-inflammatory validation step was based on the detection of reactive oxygen species (ROS) generation by activated human neutrophils. All compounds from the bioactive MIMN molecular families dose-dependently inhibited the total ROS generation promoted by fMLF (IC50: 0.04-0.42 μM), while the compounds from non-bioactive MIMN clusters did not show any significant anti-inflammatory effect. The ROS-dependent anti-inflammatory activity of these cinnamic acid glycosides was attributed to their oxygen radical scavenging ability. The most abundant cinnamic acid glycoside, angoroside C (IC50: 0.34 μM) was suggested to be selected as a chemical marker for S. ningpoensis. In this study, the MIMN platform was applied to assist in the chemical marker selection of S. ningpoensis. The correct selection of markers will aid in the compilation and revision of herbal monographs and pharmacopeias resulting in the precise analysis and classification of medicinal plants on a scientific basis.

The Skin-Whitening and Antioxidant Effects of Protocatechuic Acid (PCA) Derivatives in Melanoma and Fibroblast Cell Lines.

The skin is the most voluminous organ of the human body and is exposed to the outer environment. Such exposed skin suffers from the effects of various intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, and skin pigmentation. Skin pigmentation occurs in skin aging and is caused by hyper-melanogenesis and oxidative stress. Protocatechuic acid (PCA) is a natural secondary metabolite from a plant-based source widely used as a cosmetic ingredient. We chemically designed and synthesized PCA derivatives conjugated with alkyl esters to develop effective chemicals that have skin-whitening and antioxidant effects and enhance the pharmacological activities of PCA. We identified that melanin biosynthesis in B16 melanoma cells treated with alpha-melanocyte-stimulating hormone (α-MSH) is decreased by PCA derivatives. We also found that PCA derivatives effectively have antioxidant effects in HS68 fibroblast cells. In this study, we suggest that our PCA derivatives are potent ingredients for developing cosmetics with skin-whitening and antioxidant effects.

Unexploited Potentials of Endophytic Fungi: Patents Review on Endophytic Fungi Related to Secondary Bioactive Compounds

Pharmacognosy Research,2023,15,2,217-225.DOI:10.5530/pres.15.2.023Published:February 2023Type:Review ArticleAuthors:Priyatama V. Powar, and Shilpa Chaudhari Author(s) affiliations:Priyatama V. Powar*, Shilpa Chaudhari Department of Pharmaceutics, Dr. D. Y. Patil College of Pharmacy, Akurdi, Pune, Maharashtra, INDIA. Abstract:Endophytic fungi are various micro-organisms that inhabit intracellular or intercellular plant tissues in symbiotic association [at certain stages of their life cycles], without causing damage or morphological changes. The endophytes from medicinal plants are important resources for discovery of natural products and secondary bioactive metabolites having the potential biotechnological applications in agriculture, medicine, and allied sectors. The endophytic fungi such as Acremonium, Aspergillus, Fusarium, Trichoderma, Penicillium, Phomopsis, Pestalotiopsis, Pseudomassari, Quercina, Trichoderma genera have been reported from different medicinal plants with potential therapeutic activity. On the other hand, the endophytic fungi can also confer profound impacts on their host plants like improvement in growth, activation of systemic tolerances towards abiotic/biotic stresses, enhancement of nutrient solublization, biosynthesis of phytohormones and stimulating accumulation of secondary metabolites. Endophytic fungi have attracted much research interest because they have provided not only novel sources of Cytotoxic compounds, Antimicrobial agents, Bio-stimulants for essential oil biosynthesis, Anticancer agents, antioxidant agents, anti-diabetic agents, immunosuppressant and insecticidal compounds. The present review reveals the importance of endophytic fungi from medicinal plants as a source of bioactive compounds as well as landscape of patents related to the production of secondary metabolites through endophytic fungi and their application in pharmaceutical sectors. Keywords:Biological activity, Endophytic fungi, Patents, Phytohormones., Secondary metabolites, Symbiotic associationView:PDF (564.03 KB)