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Filariasis is a neglected tropical ailment that is among the oldest on Earth. It causes deformities and has a low fatality rate, but it causes a wide spectrum of clinical symptoms and a high morbidity rate, which causes society to stigmatise the disease. The underlying cause of this medical illness is nematode worms, which are thread-like worms that are categorised according to their presence in vertebrate hosts. Mansonella ozzardi and Onchocerca volvulus are members of the body cavity group, Brugia malayi and Brugia timori are members of the lymphatic group, and Onchocerca streptocerca and Loa loa are members of the cutaneous group. Several pathological problems accompany the mosquito-borne illness lymphatic filariasis, which is among the most common diseases in tropical and subtropical areas. Research into filariasis has advanced rapidly in recent years, shedding light on the parasite's genetics, the host-parasite dynamic, the disease's pathophysiology and the efficacy of treatment. To avoid side effects and provide permanent relief from the aforementioned filarial infections, which cannot be achieved with the marketed drug-therapy, there is a need for an alternative herbal medicinal therapy for filariasis, even though there are marketed preparations for the treatment. Consequently, the plant items that have been shown to be effective against severe filarial infections are the focus of this review. [ABSTRACT FROM AUTHOR]

SUMMARY: Triterpenoids (C30‐isoprenoids) represent a major group of natural products with various physiological functions in plants. Triterpenoids and their derivatives have medicinal uses owing to diverse bioactivities. Arjuna (Terminalia arjuna) tree bark accumulates highly oxygenated β‐amyrin‐derived oleanane triterpenoids (e.g., arjunic acid, arjungenin, and arjunolic acid) with cardioprotective roles. However, biosynthetic routes and enzymes remain poorly understood. We mined the arjuna transcriptome and conducted cytochrome P450 monooxygenase (P450) assays using Saccharomyces cerevisiae and Nicotiana benthamiana to identify six P450s and two P450 reductases for oxidative modifications of oleanane triterpenoids. P450 assays using oleananes revealed a greater substrate promiscuity of C‐2α and C‐23 hydroxylases/oxidases than C‐28 oxidases. CYP716A233 and CYP716A432 catalyzed β‐amyrin/erythrodiol C‐28 oxidation to produce oleanolic acid. C‐2α hydroxylases (CYP716C88 and CYP716C89) converted oleanolic acid and hederagenin to maslinic acid and arjunolic acid. CYP716C89 also hydroxylated erythrodiol and oleanolic aldehyde. However, CYP714E107a and CYP714E107b catalyzed oleanolic acid/maslinic acid/arjunic acid, C‐23 hydroxylation to form hederagenin, arjunolic acid and arjungenin, and hederagenin C‐23 oxidation to produce gypsogenic acid, but at a lower rate than oleanolic acid C‐23 hydroxylation. Overall, P450 substrate selectivity suggested that C‐28 oxidation is the first P450‐catalyzed oxidative modification in the arjuna triterpenoid pathway. However, the pathway might branch thereafter through C‐2α/C‐23 hydroxylation of oleanolic acid. Taken together, these results provided new insights into substrate range of P450s and unraveled biosynthetic routes of triterpenoids in arjuna. Moreover, complete elucidation and reconstruction of arjunolic acid pathway in S. cerevisiae and N. benthamiana suggested the utility of arjuna P450s in heterologous production of cardioprotective compounds. Significance Statement: Arjuna tree bark contains bioactive triterpenoids that received considerable attention as cardioprotective compounds, but the biosynthetic enzymes remained largely unknown. In this work, transcriptome mining, metabolite analysis, and enzyme biochemical characterization led to identification of six cytochrome P450 monooxygenases (CYP716A233, CYP716A432, CYP716C88, CYP716C89, CYP714E107a, and CYP714E107b) and two cognate P450 reductases (TaCPR1 and TaCPR2) that catalyzed sequential C‐2α, C‐23, and C‐28 oxidations of oleanane scaffolds for the biosynthesis of arjunic acid, arjungenin, and arjunolic acid. [ABSTRACT FROM AUTHOR]

The protein–protein interaction (PPI) network of the Mediator complex is very tightly regulated and depends on different developmental and environmental cues. Here, we present an interactive platform for comparative analysis of the Mediator subunits from humans, baker's yeast Saccharomyces cerevisiae, and model plant Arabidopsis thaliana in a user‐friendly web‐interface database called MediatorWeb. MediatorWeb provides an interface to visualize and analyze the PPI network of Mediator subunits. The database facilitates downloading the untargeted and unweighted network of Mediator complex, its submodules, and individual Mediator subunits to better visualize the importance of individual Mediator subunits or their submodules. Further, MediatorWeb offers network visualization of the Mediator complex and interacting proteins that are functionally annotated. This feature provides clues to understand functions of Mediator subunits in different processes. In an additional tab, MediatorWeb provides quick access to secondary and tertiary structures, as well as residue–level contact information for Mediator subunits in each of the three model organisms. Another useful feature of MediatorWeb is detection of interologs based on orthologous analyses, which can provide clues to understand the functions of Mediator complex in less explored kingdoms. Thus, MediatorWeb and its features can help the user to understand the role of Mediator complex and its subunits in the transcription regulation of gene expression. [ABSTRACT FROM AUTHOR]