Stilbenes: a journey from folklore to pharmaceutical innovation.

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi.

Development and characterization of rice bran-gum Arabic based encapsulated biofertilizer for enhanced shelf life and controlled bacterial release.

Introduction: Currently, microbe-based approaches are being tested to address nutrient deficiencies and enhance nutrient use efficiency in crops. However, these bioinoculants have been unsuccessful at the commercial level due to differences in field and in-vivo conditions. Thus, to enhance bacterial stability, microbial formulations are considered, which will provide an appropriate microenvironment and protection to the bacteria ensuring better rhizospheric-colonization. Methods: The present study aimed to develop a phosphobacterium-based encapsulated biofertilizer using the ion-chelation method, wherein a bacterial strain, Myroid gitamensis was mixed with a composite solution containing rice bran (RB), gum Arabic (GA), tricalcium phosphate, and alginate to develop low-cost and slow-release microbeads. The developed microbead was studied for encapsulation efficiency, shape, size, external morphology, shelf-life, soil release behavior, and biodegradability and characterized using SEM, FTIR, and XRD. Further, the wheat growth-promoting potential of microbeads was studied. Results: The developed microbeads showed an encapsulation efficiency of 94.11%. The air-dried beads stored at 4°C were favorable for bacterial survival for upto 6 months. Microbeads showed 99.75% degradation within 110 days of incubation showing the bio-sustainable nature of the beads. The application of dried formulations to the pot-grown wheat seedlings resulted in a higher germination rate, shoot length, root length, fresh weight, dry weight of the seedlings, and higher potassium and phosphorus uptake in wheat. Discussion: This study, for the first time, provides evidence that compared to liquid biofertilizers, the RB-GA encapsulated bacteria have better potential of enhancing wheat growth and can be foreseen as a future fertilizer option for wheat.

Harnessing the action mechanisms of microbial endophytes for enhancing plant performance and stress tolerance: current understanding and future perspectives.

Microbial endophytes are microorganisms that reside within plant tissues without causing any harm to their hosts. These microorganisms have been found to confer a range of benefits to plants, including increased growth and stress tolerance. In this review, we summarize the recent advances in our understanding of the mechanisms by which microbial endophytes confer abiotic and biotic stress tolerance to their host plants. Specifically, we focus on the roles of endophytes in enhancing nutrient uptake, modulating plant hormones, producing secondary metabolites, and activating plant defence responses. We also discuss the challenges associated with developing microbial endophyte-based products for commercial use, including product refinement, toxicology analysis, and prototype formulation. Despite these challenges, there is growing interest in the potential applications of microbial endophytes in agriculture and environmental remediation. With further research and development, microbial endophyte-based products have the potential to play a significant role in sustainable agriculture and environmental management.

Emergence of toxic trace elements in plant environment: Insights into potential of silica nanoparticles for mitigation of metal toxicity in plants.

Emergence of trace elements at potentially toxic concentrations in the environment has become a global issue in recent times. Owing to the rapid population growth, unregulated industrialisation, intensive farming practices and excessive mining activities, these elements are accumulating in environment at high toxic concentrations. The exposure of plants to metal-contaminated environments severely influences their reproductive and vegetative growth, eventually affecting crop performance and production. Hence, it is crucial to find alternatives to mitigate the stress caused by toxic elements, in plants of agricultural importance. In this context, silicon (Si) has been widely recognized to alleviate metal toxicity and promote plant growth during various stress conditions. Amending soil with silicates has shown to ameliorate the lethal effects of metals and stimulates crop development. However, in comparison to silicon in bulk form, nano-sized silica particles (SiNPs) have been demonstrated to be more efficient in their beneficial roles. SiNPs can be used for various technological applications, viz. Improving soil fertility, agricultural yield, and remediating heavy metal-polluted soil. The research outcomes of studies focussing on role of silica nanoparticles to specifically mitigate the metal toxicity in plants have not been reviewed earlier in depth. The aim of this review is to explore the potential of SiNPs in alleviating metal stress and improving plant growth. The benefits of nano-silica over bulk-Si fertilizers in farming, their performance in diverse plant varieties, and the possible mechanisms to mitigate metal toxicity in plants have been discussed in detail. Further, research gaps are identified and future prospects are envisioned for advanced investigations in this field. The growing interest towards nano-silica related research will facilitate exploration of the true prospective of these nanoparticles for mitigation of metal stress in crops and in other fields of agriculture as well.

Purification of ursolic acid and ß-sitosterol from endophytic Alternaria alternata for their alpha-amylase inhibitory activity.

Fungal endophytes are a known warehouse of bioactive compounds with multifarious applications. In the present investigation two compounds, ß-Sitosterol (1) and ursolic acid (2), were isolated from Alternaria alternata, an endophytic fungus associated with Morus alba Linn for the first time. The structure of the compounds was elucidated on the basis of comprehensive spectral analysis (UV, IR, 1 H-, 13 C- and 2D-NMR, as well as HRESI-MS). In the in vitro alpha amylase inhibitory assay both compounds (1) and (2) show potent antidiabetic activity. In support, Docking studies indicate significant binding affinity of the isolated compounds. Hence from the present study, it can be concluded that endophytic fungi in Morus alba Linn can find use in antidiabetic drug development in the medicinal industry.Communicated by Ramaswamy H. Sarma.

'A plant's major strength in rhizosphere': the plant growth promoting rhizobacteria.

Human activities, industrialization and civilization have deteriorated the environment which eventually has led to alarming effects on plants and animals by heightened amounts of chemical pollutants and heavy metals in the environment, which create abiotic stress. Environmental conditions like drought, salinity, diminished macro-and micro-nutrients also contribute in abiotic stress, resulting in decrement of survival and growth of plants. Presence of pathogenic and competitive microorganisms, as well as pests lead to biotic stress and a plant alone can not defend itself. Thankfully, nature has rendered plant's rhizosphere with plant growth promoting rhizobacteria which maintain an allelopathic relationship with host plant to defend the plant and let it flourish in abiotic as well as biotic stress situations. This review discusses the mechanisms behind increase in plant growth via various direct and indirect traits expressed by associated microorganisms in the rhizosphere, along with their current scenario and promising future for sustainable agriculture. It also gives details of ten such bacterial species, viz. Acetobacter, Agrobacterium, Alcaligenes, Arthrobacter, Azospirillum, Azotobacter, Bacillus, Burkholderia, Enterobacter and Frankia, whose association with the host plants is famed for enhancing plant's growth and survival.

Preparation and antibacterial mechanism of cinnamaldehyde/tea polyphenol/polylactic acid coaxial nanofiber films with zinc oxide sol to Shewanella putrefaciens.

In this study, the coaxial nanofiber films were prepared by coaxial electrospinning technique with cinnamaldehyde (CMA) and tea polyphenol (TP) as core material and polylactic acid (PLA) as shell material, and to obtain food packaging materials with great physicochemical and antibacterial properties, zinc oxide (ZnO) sol were added into PLA, and ZnO/CMA/TP-PLA coaxial nanofiber films were prepared. Meanwhile, the microstructure and physicochemical properties were determined, and the antibacterial properties and mechanism were investigated with Shewanella putrefaciens (S. putrefaciens) as target. The results show that the ZnO sol makes the physicochemical properties and antibacterial properties of the coaxial nanofiber films improve. Among them, the 1.0 % ZnO/CMA/TP-PLA coaxial nanofibers have smooth and continuous uniform surfaces, and their encapsulation effect on CMA/TP and antibacterial properties are the optimal. The synergistic action of CMA/TP and ZnO sol cause severe depression and folding of the cell membrane of S. putrefaciens, makes cell membrane permeability increase and of intracellular materials spillage, interference the bacteriophage protein expression, and makes macromolecular protein degraded. In this study, the introduction of oxide sols into polymeric shell materials by in-situ synthesis technique can provide theoretical support and methodological guidance for the application of electrospinning technology in the field of food packaging.

Key insights into secondary metabolites from various Chaetomium species.

Endophytic fungi have proved to be a major source of secondary metabolites, wherein the genus Chaetomium has emerged as a source of multifarious bioactive natural compounds belonging to diverse classes such as chaetoglobosins, epipolythiodioxopiperazines, azaphilones, xanthones, anthraquinone, chromones, depsidones, terpenoids, and steroids. The objective of this review is to encapsulate recent findings on various Chaetomium strains, such as C. globosum, C. cupreum, C. elatum, C. subspirale, C. olivaceum, C. indicum, and C. nigricolor known for production of beneficial secondary metabolites, with an insight into their origin and function. A thorough literature survey was conducted for obtaining Chaetomium-derived secondary metabolites, with a scope of future application into drug development efforts. More than 100 secondary metabolites, with various beneficial properties such as antitumor, cytotoxic, antimalarial, and enzyme inhibitory activities, were enlisted. We believe this review will enhance the understanding of beneficial effects conferred by various Chaetomium-derived secondary metabolites and emphasize their potential in serving novel drug development efforts. KEY POINTS: • Identified Chaetomium-derived metabolites with potential for drug development. • More than 100 beneficial metabolites are enlisted. • Benefits include anti-cancerous, antimalarial, and anti-enzymatic properties.

Response Surface Optimization for Investigating Antioxidant Potential of Camellia Sinensis and Withania Somnifera in Synergistic Manner.

The paper highlights the synergistic potential of the novel combination of Camellia sinensis (Kangra green tea) and Withania somnifera (Ashwagandha). One variable at a time approach was used to find antioxidant potential of C. sinensis and W. somnifera alone and in combination. Optimization of antioxidant potential was done by using different plant concentrations of C. sinensis and W. somnifera using a statistical approach of central composite design (CCD) of RSM (response surface methodology). Initial antioxidant activity during optimization of the solvent system was observed in methanol for C. sinensis with DPPH, superoxide radical scavenging assay and hydrogen peroxide scavenging assay (44.9 ± 0.62, 43.77 ± 0.10, 43.88 ± 0.10% scavenging) and for W. somnifera (40.22 ± 0.39, 43.29 ± 1.12, 41.88 ± 0.11% scavenging), respectively. Initially, IC50 has been calculated for C. sinensis (235.26 ± 0.012 µg/mL) and W. somnifera (256.39 ± 0.43 µg/mL) in methanol. Before statistical optimization, the maximum synergistic antioxidant potential of C. sinensis (200 µg/mL) and W. somnifera (150 µg/mL) with DPPH assay, superoxide radical scavenging and hydrogen peroxide scavenging assay was found to be 56.57 ± 0.62, 56.99 ± 0.42, 55.44 ± 0.53% scavenging, respectively. IC50 value has been calculated for C. sinensis + W. somnifera (IC50 = 215.47 ± 0.06 µg/mL). Optimization of plant concentration using CCD of RSM resulted in enhancement of antioxidant potential of C. sinensis (200.5 µg/mL) and W. somnifera (200.5 µg/mL) was found to be 78.01 ± 0.01% scavenging when compared to the initial antioxidant potential, i.e., 56.57 ± 0.62% scavenging shows a 1.37-fold increase from initial antioxidant potential. Research unveils that using various combination of C. sinensis and W. somnifera enhance the antioxidant potential in vitro. Supplementary Information: The online version contains supplementary material available at 10.1007/s40011-022-01423-6.

Isolation of Alpha Amylase-Producing Bacteria from Local Region of Ambala and Production of Amylase Under Optimized Factors Using Solid-State Fermentation.

Enzymes are one of the most significant products produced primarily from microbial sources for human requirements. The purpose of this work was to isolate, screen, and optimize enzyme production under solid-state fermentation. In the present study, amylase-producing bacteria were isolated from the local region of Ambala. A total of six samples were taken, out of which 14 isolates were isolated, among which seven isolates were found to be amylase producing. Highest amylase yield was obtained from isolate A11, further studied for the production of amylase under solid substrate fermentation (SSF), and also optimized the conditions for increased production of amylase. The molecular and biochemical characterization confirmed it as a strain of Alkalihalobacillus clausii. It was observed that growth parameters showed a profound effect on the production. The bacterium produces ample amount (7.3 × 103 IU/g) of alpha amylase using wheat bran using OVAT (one variable at a time) approach. Further using RSM (Response Surface Methodology) resulted in 3.78-fold increase in alpha amylase production, i.e., 27.57 × 103 IU/g.

Microbial endophytes: application towards sustainable agriculture and food security.

Microbial endophytes are ubiquitous and exist in each recognised plant species reported till date. Within the host plant, the entire community of microbes lives non-invasively within the active internal tissues without causing any harm to the plant. Endophytes interact with their host plant via metabolic communication enables them to generate signal molecules. In addition, the host plant's genetic recombination with endophytes helps them to imitate the host's physicochemical functions and develop identical active molecules. Therefore, when cultured separately, they begin producing the host plant phytochemicals. The fungal species Penicillium chrysogenum has portrayed the glory days of antibiotics with the invention of the antibiotic penicillin. Therefore, fungi have substantially supported social health by developing many bioactive molecules utilised as antioxidant, antibacterial, antiviral, immunomodulatory and anticancerous agents. But plant-related microbes have emanated as fountainheads of biologically functional compounds with higher levels of medicinal perspective in recent years. Researchers have been motivated by the endless need for potent drugs to investigate alternate ways to find new endophytes and bioactive molecules, which tend to be a probable aim for drug discovery. The current research trends with these promising endophytic organisms are reviewed in this review paper. KEY POINTS: • Identified 54 important bioactive compounds as agricultural relevance • Role of genome mining of endophytes and "Multi-Omics" tools in sustainable agriculture • A thorough description and graphical presentation of agricultural significance of plant endophytes.

Inhibitory activities of grape bioactive compounds against enzymes linked with human diseases.

A quest for identification of novel, safe and efficient natural compounds, as additives in the modern food and cosmetic industries, has been prompted by concerns about toxicity and side effects of synthetic products. Plant phenolic compounds are one of the most documented natural products due to their multifarious biological applications. Grape (Vitis vinifera) is an important source of phenolic compounds such as phenolic acids, tannins, quinones, coumarins and, most importantly, flavonoids/flavones. This review crisply encapsulates enzyme inhibitory activities of various grape polyphenols towards different key human-ailment-associated enzymes: xanthine oxidase (gout), tyrosinase (hyperpigmentation), α-amylase and α-glucosidase (diabetes mellitus), pancreatic lipase (obesity), cholinesterase (Alzheimer's disease), angiotensin i-converting enzymes (hypertension), α-synuclein (Parkinson's disease) and histone deacetylase (various diseases). The review also depicts the enzyme inhibitory mechanism of various grape polyphenols and briefly discusses their stature as potential therapeutic and drug development candidates. KEY POINTS: • Nineteen major bioactive polyphenols from the grape/grape products and their disease targets are presented • Sixty-two important polyphenols as enzyme inhibitors from grape/grape products are presented • A thorough description and graphical presentation of biological significance of polyphenols against various diseases.

Effect of precursor feeding, dietary supplementation, chemical elicitors and co-culturing on resveratrol production by Arcopilus aureus.

Resveratrol is an important stilbene, initially identified from red wine possessing immense therapeutic, cosmeceutical and nutraceutical applications. In the present study, endophytic fungus Arcopilus aureus(#12VVLMP) which produces resveratrol extracellularly was selected as a candidate for epigenetic modulation using natural supplements, precursor feeding, chemical elicitors and co-culturing to enhance resveratrol production. The present study highlighted the role of natural supplements i.e. grape seed extract and grape skin extract which constitute grape pomace to enhance resveratrol production by 27.7 and 13.65% respectively. Co-culturing also impacted the resveratrol production by A. aureus, enhancing it by 9.4%. Chemical elicitors and precursor feeding did not induce significant enhancement in resveratrol production. Enhancement of anti-oxidant effect was also observed in the case of use of natural supplements assayed by DPPH and ABTS• radical scavenging assays. Similarly anti-staphylococcal and anti-candida activities were potentially higher when natural supplements were used followed by co-culturing. These findings indicate that the use of natural supplement which is a by-product of wine industry may be used as a modulator of resveratrol production by A. aureus. This shall lead to a cost-effective fermentation process of resveratrol production, the global demand of which is continuously increasing.

Response surface statistical optimization of fermentation parameters for resveratrol production by the endophytic fungus Arcopilus aureus and its tyrosinase inhibitory activity.

OBJECTIVE: The present investigation primarily focusses on enhancement of resveratrol production by endophytic production from the endophytic fungus, Arcopilus aureus via one variable at a time approach (OVAT) followed by statistical approach using response surface methodology (RSM). The paper also highlights the characterization of fungal resveratrol using spectroscopic techniques. Further the tyrosinase inhibitory property was also explored in this communication for its possible use as a cosmeceutical ingredient. RESULTS: Optimization of physicochemical and nutritional parameters using OVAT approach exhibited 1.23-fold enhancement in production of resveratrol when compared to initial yield, 89.1 ± 0.08 µg/mL. Further RSM resulted in 1.49-fold enhancement in resveratrol production i.e. 133.53 µg/ml. Further, 25 mg of fungal resveratrol in pure form was obtained from the spent broth of Arcopilus aureus by column chromatography using a mobile phase comprising of MeOH: DCM in a ratio of 1.75:98.25. Further its purity on TLC was checked using 5% MeOH: DCM as mobile phase. Symmetrical peak with Rt of 3.36 min using a C18 reverse phase column confirmed the homogeneity of the purified fungal resveratrol with standard resveratrol and further corroborated by 1H-NMR, 13C-NMR and HR-MS analysis. Fungal resveratrol exhibited a good tyrosinase inhibition with an IC50 of 2.654 ± 0.432 µg/mL as compared to Kojic acid (1.329 ± 0.333). CONCLUSIONS: The present study has provided sufficient lead that process optimization techniques can complement each other for optimized production of bioactive compounds by microorganisms apart from strain improvement techniques which are generally adopted in the industry. The enhancement of resveratrol production by Arcopilus aureus by process optimization further opens up avenues for strain improvement for commercial resveratrol production through fermentation for nutraceutical and cosmeceutical applications.

Diversity and phylogeny of resveratrol-producing culturable endophytic fungi from Vitis species in India.

In the present study, resveratrol producing culturable endophytes were recovered from the Indian vineyards. Of the 145 endophytic fungi recovered, only 30.3% were positive for resveratrol production in the preliminary screening. Culture broth of only 13 isolates exhibited the actual presence of resveratrol in the range of 4.4-52.3 µg/ml by HPLC quantification. The most potent endophytic isolate producing the highest extracellular resveratrol was #19VVLPM isolated from the Pinot Noir variety. Further LC-MS analysis confirmed the similarity of fungal resveratrol with standard resveratrol. The Merlot variety exhibited the highest colonization frequency of the resveratrol-producing fungal endophytes. Using morphological methods as well as molecular phylogeny #19VVLPM was identified as Fusarium equiseti. It is a promising candidate for further development into a commercial strain.

Isolation and enhancement of resveratrol production in Xylaria psidii by exploring the phenomenon of epigenetics: using DNA methyltransferases and histone deacetylase as epigenetic modifiers.

Resveratrol is an important stilbene which is having a high demand due to its therapeutic, cosmeceutical and nutraceutical activities. The current study mainly focuses on strategies to enhance the fungal potential to produce resveratrol via the activation of the cryptic biosynthetic pathway with their particular interest in the antioxidant application. The endophytic fungus Xylaria psidii was isolated from the surface sterilized leaf of Vitis vinifera. With the help of HPLC analysis it is found that resveratrol concentration was maximum and enhanced in case of treatment with 5 µm SAHA (52.32 µg/mL) and by 10 µm AZA (48.94 µg/mL) followed by 10 µm SAHA (41.10 µg/mL) and 5 µm AZA (37.72 µg/mL). After treatment with different concentration of epigenetic modifiers such as HDAC inhibitors (SAHA) and dMNTs (AZA) inhibitors, a significant increase in antioxidant potential was obtained. In the case of DPPH increase in scavenging potential was found as compared to wild strain. Treatment with 5 µm SAHA and by 10 µm AZA was showing strong antioxidant potential among all the epigenetic variants as compared to wild strain. In the case of TEAC also the same trend as in the case of DPPH was obtained.

Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae.

Two new compounds, lasdiplactone (1) and lasdiploic acid (2) and one known compound 3 were isolated from the chloroform extract of cell free filtrate of the endophytic fungus Lasiosdiplodia pseudotheobromae. The structures of new compounds were determined by interplay of spectral techniques (IR, mass, 1H NMR, 13C NMR, DEPT, and 2D NMR). The absolute configuration at C-4 position of 1 was established as S using a process similar to modified Mosher's method. The absolute configuration of 2 was established by comparing its ECD spectrum with the calculated ECD spectra of all possible isomers. In the in vitro XO inhibition assay, the highest inhibition was exhibited by 3 with an IC50 of 0.38 ±â€¯0.13 µg/ml, followed by 2 with an IC50 of 0.41 ±â€¯0.1 µg/ml and the least in 1. The oxidized form of 1 also showed high XO inhibition with IC50 of 0.35 ±â€¯0.13 µg/ml.

Arcopilus aureus, a Resveratrol-Producing Endophyte from Vitis vinifera.

Resveratrol is extensively being used as a therapeutic moiety, as well as a pharmacophore for development of new drugs due to its multifarious beneficial effects. The objective of the present study was to isolate and screen the resveratrol-producing endophytic fungi from different varieties of Vitis vinifera. A total of 53 endophytic fungi belonging to different fungal genera were isolated from the stem and leaf tissues of Vitis vinifera (merlot, wild, pinot noir, Shiraz, muscat) from different grape-producing locations of India. Only 29 endophytic fungal isolates exhibited a positive test for phenolics by phytochemical methods. The resveratrol obtained after ethyl acetate extraction was confirmed using standard molecule on thin layer chromatography (TLC) with a retention factor (Rf) of 0.69. The purified and standard resveratrol were visualized under UV light as a violet-colored spot. In HPLC analysis of the ethyl acetate extract of culture broth of 11 endophytic isolates, the highest resveratrol content was found in #12VVLPM (89.1 µg/ml) followed by #18VVLPM (37.3 µg/ml) and 193VVSTPM (25.2 µg/ml) exhibiting a retention time of 3.36 min which corresponded to the standard resveratrol. The resveratrol-producing isolates belong to seven genera viz. Aspergillus, Botryosphaeria, Penicillium, Fusarium, Alternaria, Arcopilus, and Lasiodiplodia, and using morphological and molecular methods, #12VVLPM was identified as Arcopilus aureus.