Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19.

COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19.

Traditional uses, phytochemistry, pharmacology, and toxicology of the genus Artemisia L. (Asteraceae): A high-value medicinal plant.

Biologically active secondary metabolites, essential oils, and volatile compounds derived from medicinal and aromatic plants play a crucial role in promoting human health. Within the large family Asteraceae, the genus Artemisia consists of approximately 500 species. Artemisia species have a rich history in traditional medicine worldwide, offering remedies for a wide range of ailments, such as malaria, jaundice, toothache, gastrointestinal problems, wounds, inflammatory diseases, diarrhoea, menstrual pains, skin disorders, headache, and intestinal parasites. The therapeutic potential of Artemisia species is derived from a multitude of phytoconstituents, including terpenoids, phenols, flavonoids, coumarins, sesquiterpene lactones, lignans, and alkaloids that serve as active pharmaceutical ingredients (API). The remarkable antimalarial, antimicrobial, anthelmintic, antidiabetic, anti-inflammatory, anticancer, antispasmodic, antioxidative and insecticidal properties possessed by the species are attributed to these APIs. Interestingly, several commercially utilized pharmaceutical drugs, including arglabin, artemisinin, artemether, artesunate, santonin, and tarralin have also been derived from different Artemisia species. However, despite the vast medicinal potential, only a limited number of Artemisia species have been exploited commercially. Further, the available literature on traditional and pharmacological uses of Artemisia lacks comprehensive reviews. Therefore, there is an urgent need to bridge the existing knowledge gaps and provide a scientific foundation for future Artemisia research endeavours. It is in this context, the present review aims to provide a comprehensive account of the traditional uses, phytochemistry, documented biological properties and toxicity of all the species of Artemisia and offers useful insights for practitioners and researchers into underutilized species and their potential applications. This review aims to stimulate further exploration, experimentation and collaboration to fully realize the therapeutic potential of Artemisia in augmenting human health and well-being.

An assessment of the physicochemical characteristics and essential oil composition of Mentha longifolia (L.) Huds. exposed to different salt stress conditions.

Salt stress adversely influences growth, development, and productivity in plants, resulting in a limitation on agriculture production worldwide. Therefore, this study aimed to investigate the effect of four different salts, i.e., NaCl, KCl, MgSO4, and CaCl2, applied at various concentrations of 0, 12.5, 25, 50, and 100 mM on the physico-chemical properties and essential oil composition of M. longifolia. After 45 days of transplantation, the plants were irrigated at different salinities at 4-day intervals for 60 days. The resulting data revealed a significant reduction in plant height, number of branches, biomass, chlorophyll content, and relative water content with rising concentrations of NaCl, KCl, and CaCl2. However, MgSO4 poses fewer toxic effects than other salts. Proline concentration, electrolyte leakage, and DPPH inhibition (%) increase with increasing salt concentrations. At lower-level salt conditions, we had a higher essential oil yield, and GC-MS analysis reported 36 compounds in which (-)-carvone and D-limonene covered the most area by 22%-50% and 45%-74%, respectively. The expression analyzed by qRT-PCR of synthetic Limonene (LS) and Carvone (ISPD) synthetic genes has synergistic and antagonistic relationships in response to salt treatments. To conclude, it can be said that lower levels of salt enhanced the production of essential oil in M. longifolia, which may provide future benefits commercially and medicinally. In addition to this, salt stress also resulted in the emergence of novel compounds in essential oils, for which future strategies are needed to identify the importance of these compounds in M. longifolia.

Changing Rhizosphere Microbial Community and Metabolites with Developmental Stages of Coleus barbatus.

Coleus barbatus is a medicinal herb belonging to Lamiaceae. It is the only living organism known to produce forskolin, which is a labdane diterpene and is reported to activate adenylate cyclase. Microbes associated with plants play an important role in maintaining plant health. Recently, the targeted application of beneficial plant-associated microbes and their combinations in abiotic and biotic stress tolerance has gained momentum. In this work, we carried out the rhizosphere metagenome sequencing of C. barbatus at different developmental stages to understand how rhizosphere microflora are affected by and affect the metabolite content in plants. We found that the Kaistobacter genus was abundantly present in the rhizosphere of C. barbatus and its accumulation pattern appears to correlate with the quantities of forskolin in the roots at different developmental stages. Members of the Phoma genus, known for several pathogenic species, were in lower numbers in the C. barbatus rhizosphere in comparison with C. blumei. To our knowledge, this is the first metagenomic study of the rhizospheric microbiome of C. barbatus, which may help to explore and exploit the culturable and non-culturable microbial diversity present in the rhizosphere.

Transcriptome analysis and differential expression in Arabidopsis thaliana in response to rohitukine (a chromone alkaloid) treatment.

Rohitukine is a chromone alkaloid and precursor of potent anticancer drugs flavopiridol, P-276-00, and 2,6-dichloro-styryl derivative (11d) (IIIM-290). The metabolite is reported to possess anticancer, anti-inflammatory, antiadipogenic, immunomodulatory, gastroprotective, anti-implantation, antidyslipidemic, anti-arthritic, and anti-fertility properties. However, the physiological role of rohitukine in plant system is yet to be explored. Here, we studied the effect of rohitukine isolated from Dysoxylum gotadhora on Arabidopsis thaliana. The A. thaliana plants grown on a medium fortified with different rohitukine concentrations showed a significant effect on the growth and development. The root growth of A. thaliana seedlings showed considerable inhibition when grown on medium containing 1.0 mM of rohitukine. Transcriptomic analysis indicated the expression of 895 and 932 genes in control and treated samples respectively at a cut-off of FPKM ≥ 1 and P-value < 0.05. Gene ontology (GO) analysis revealed the upregulation of genes related to photosynthesis, membrane transport, antioxidation, xenobiotic degradation, and some transcription factors (TFs) in response to rohitukine. Conversely, rohitukine downregulated several genes including RNA helicases and those involved in nitrogen compound metabolism. The RNA-seq result was also validated by real-time qRT-PCR analysis. In light of these results, we discuss (i) likely ecological importance of rohitukine in parent plant as well as (ii) comparison between responses to rohitukine treatment in plants and mammals.

Exogenously Applied Rohitukine Inhibits Photosynthetic Processes, Growth and Induces Antioxidant Defense System in Arabidopsis thaliana.

The secondary metabolite rohitukine has been reported in only a few plant species, including Schumanniophyton magnificum, S. problematicum, Amoora rohituka, Dysoxylum acutangulum and D. gotadhora. It has several biological activities, such as anticancer, anti-inflammatory, antiadipogenic, immunomodulatory, gastroprotective, anti-implantation, antidyslipidemic, anti-arthritic and anti-fertility properties. However, the ecological and physiological roles of rohitukine in parent plants have yet to be explored. Here for the first time, we tried to decipher the physiological effect of rohitukine isolated from D. gotadhora on the model system Arabidopsis thaliana. Application of 0.25 mM and 0.5 mM rohitukine concentrations moderately affected the growth of A. thaliana, whereas a remarkable decrease in growth and the alteration of various morphological, physiological and biochemical mechanisms were observed in plants that received 1.0 mM of rohitukine as compared to the untreated control. A. thaliana showed considerable dose-dependent decreases in leaf area, fresh weight and dry weight when sprayed with 0.25 mM, 0.5 mM and 1.0 mM of rohitukine. Rohitukine exposure resulted in the disruption of photosynthesis, photosystem II (PSII) activity and degradation of chlorophyll content in A. thaliana. It also triggered oxidative stress in visualized tissues through antioxidant enzyme activity and the expression levels of key genes involved in the antioxidant system, such as superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX). Rohitukine-induced changes in levels of metabolites (amino acids, sugars, organic acids, etc.) were also assessed. In light of these results, we discuss (i) the likely ecological importance of rohitukine in parent plants as well as (ii) the comparison of responses to rohitukine treatment in plants and mammals.

Plant growth promoting potential of butyl isobutyl phthalate and Streptomyces sp. from Rumex dentatus on rice.

Rice (Oryza sativa L.) is one of the most important staple foods consumed in many countries of the world. It is mostly consumed in developing countries where different chemical fertilizers are used to improve the productivity of the crop plant. In the present study, endophytic actinomycetes isolated from Rumex dentatus were identified morphologically and by scanning electron microscopy. Butyl isobutyl phthalate (BIBP) was isolated from the root endophyte Streptomyces sp. JR9 using column chromatography and HPLC methods. The compound was tested for its effect on rice seed germination. BIBP, extracts, and isolates were evaluated for their plant growth effect on rice in a growth chamber. Isolates were also screened in vitro for phosphate solubilization activity and enzyme production. Indole-3-acetic acid (IAA) and BIBP produced in extracts were quantified and detected using high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) methods, respectively. BIBP was found to increase the germination of rice seeds by 6 to 12% in treated samples and displayed potent effect at lowest concentration (0.437 µM). Both the compound and the extract depicted significant increases in almost all growth parameters at lowest concentration of 0.125 µg/mL and 62.5 µg/mL, respectively. BIBP also increased significantly shoot length, fresh root, fresh shoot, and dried shoot weight at high concentrations and was more potent than the standard phytohormone IAA. HPLC quantification showed 7.952 µg/mg and 0.371 µg/mg of IAA in extracts of Streptomyces sp. JR9 and the stem endophyte Streptomyces sp. KS3, respectively. IAA containing extract of JR9 increased significantly most growth parameters at lowest concentration (125 µg/mL). The extract of KS3 depicted significant increases in almost all growth parameters at high concentration (500 µg/mL). Our investigation showed that streptomycetes isolated from R. dentatus and BIBP are potent growth promoting agents and can be used in agriculture as bio-fertilizer to improve the growth and productivity of rice. KEY POINTS: • Butyl isobutyl phthalate (BIBP) isolated from endophytic Streptomyces sp. JR9 is a potent rice seed germination activator and promotes significantly the growth of rice • Isolated endophytes showed the ability to produce enzymes and phytohormone IAA • Isolates enhanced significantly the growth of rice.

Exogenously-applied L-glutamic acid protects photosynthetic functions and enhances arsenic tolerance through increased nitrogen assimilation and antioxidant capacity in rice (Oryza sativa L.).

L-Glutamic acid (Glu) is used as an effective bio-stimulant to reduce arsenic (As) stress in plants. The role of Glu was studied in the protection of photosynthesis and growth of rice (Oryza sativa L. Japonica Type Taipie-309) plants grown with 50 µM As stress by studying the oxidative stress, photosynthetic and growth characteristics. Among the Glu concentrations (0, 2.5, 5 and 10 µM), 10 µM Glu maximally enhanced photosynthesis and growth parameters with the least cellular oxidative stress level. The supplementation of 10 µM Glu resulted in the reduced effects of As stress on gas exchange parameters, PSII activity and growth attributes through enhancement of antioxidant and proline metabolism. The enzymes of nitrogen (N) assimilation, such as nitrate reductase, nitrite reductase, glutamine synthetase and glutamate synthase were increased with Glu treatment under As stress. The Glu-induced metabolite synthesis showed the role of various metabolites in As stress responses. The role of Glu as a signalling molecule in reducing the adverse effects of As through accelerating the antioxidant enzymes, PSII activity, proline metabolism and nitrogen assimilation has been discussed.

Plant aquaporins: A frontward to make crop plants drought resistant.

Drought stress alters gene expression and causes cellular damage in crop plants. Drought inhibits photosynthesis by reducing the content and the activity of the photosynthetic carbon reduction cycle, ultimately decreasing the crop yield. The role of aquaporins (AQP) in improving the growth and adaptation of crop plants under drought stress is of importance. AQP form channels and control water transport in and out of the cells and are associated with drought tolerance mechanisms. The current review addresses: (1) the evolution of AQPs in plants, (2) the classification of plant AQPs, (3) the role of AQPs in drought alleviation in crop plants, and (4) the phytohormone crosstalk with AQPs in crops exposed to drought stress.

Hydrogen peroxide modulates activity and expression of antioxidant enzymes and protects photosynthetic activity from arsenic damage in rice (Oryza sativa L.).

We studied the role of H2O2 in the protection of photosynthesis from arsenic (As) damage in rice (Oryza sativa L.) by examining the antioxidant system, photosynthesis, and growth attributes. Among the As concentrations (0, 20, 30, 40 and 50 µM) tested, maximum oxidative stress and inhibition in photosynthesis and growth were found with 50 µM As. The application of 50 µM H2O2 resulted in alleviation of the adverse effects of 50 µM As on Pigment System (PS) II activity, photosynthesis, and growth. Hydrogen peroxide supplementation induced the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione reductase (GR) and increased reduced glutathione (GSH) content and proline metabolism. The expression of SOD and APX, PSBA and PSBB was induced in the presence of H2O2 to alleviate the As damage to PS II and maintain photosynthetic activity. The role of H2O2 as a signaling molecule is shown in the protection of photosynthetic activity in rice from As toxicity through regulation on the activity and the expression of antioxidant enzymes.

Immunohistochemical assessment for Cdx2 expression in the Barrett metaplasia-dysplasia-adenocarcinoma sequence.

BACKGROUND: Barrett oesophagus (BO) occurs as a consequence of prolonged gastro-oesophageal reflux and it may precede the development of oesophageal adenocarcinoma. AIMS: The aim of this study was to accurately assess Cdx2 expression in the oesophageal metaplasia-dysplasia-adenocarcinoma sequence. METHOD: The expression of the transcription factor Cdx2 in Barrett metaplasia, high-grade glandular dysplasia and adenocarcinoma was investigated using immunohistochemistry. RESULTS: The results confirmed previous immunohistochemistry and PCR-based investigations, indicating that Cdx2 was expressed by intestinal metaplasia in the oesophagus. In addition, upregulation followed by linear downregulation of Cdx2 expression through the oesophageal metaplasia-dysplasia-adenocarcinoma sequence was demonstrated for the first time. CONCLUSION: Such downregulation of Cdx2 expression could be in keeping with a role as a tumour suppressor gene, but a simpler explanation would be downregulation of a differentiation marker.

Angiolipoma of hypopharynx: A diagnostic dilemma.

Fibro vascular polyps of esophagus are rare tumours. They usually arise close to cricopharyngeus muscle. The commonest symptom is dysphagia but regurgitation of fleshy mass into mouth, regurgitation of recently digested food and sensation of lump in throat are also reported. Several reports of polyp regurgitation and subsequent airway obstruction are mentioned. We present a 48-year-old male with fibrovascular polyp of hypopharynx. Diagnosis was established by barium swallow and oesophagoscopy.Transoral route was used to remove the polyp and histopathology reported as angiolipoma.