Abstract

Critically endangered Aquilaria malaccensis Lam. is known for highly expensive agarwood with unique aroma. Agarwood has been used as a phytomedicine in chronic degenerative neurological disorders, paralysis, rheumatism, asthma, and others. Its production is dependent naturally or artificially on interaction of endophytic fungi, and by nailing, drilling, and microbial inoculation respectively. The majorly produced biomarkers of terpenes, fatty acids, alkanes, chromones, and flavonoids exhibited several biological activities in congruence to their ethnomedicinal claims. During the pandemic, several in-silico , studies showed the potential of a few sesquiterpene hydrocarbons against covid-19. The review aimed to deliver a comprehensive outline of the immunomodulatory potential of agarwood oil with allied traditional medicinal use, biomarkers, pharmacological evaluation, toxicity, and mechanistic action . The review eventually showed the agarwood oil, extracts, and major biomarkers viz., aromadendrene II, valencene, phytol, octacosane, caryophyllene oxide, β-caryophyllene, hinesol, agarospirol, with immunomodulatory, anti-inflammatory, and allied neural, antidiabetic, antimicrobial activity, toxicity, along with molecular target binding potential against 3CLpro, RDRP, Mpro, PLpro, Spike protein S1 of SARS-CoV2 through in-vitro, in-vivo, in silico studies and limited human clinical trials. The expression of HMGR, ASS, ADXPS, ADXPR, FPS , and WRKY genes of sesquiterpenoid biosynthetic pathways were upregulated for signature aroma and immunomodulatory markers viz., δ-guaiene, dodecane, tetracosane, agarospirol, farnesol, and geranylgeraniol acetate as a defensive response. The review would ignite future research on potential immunomodulatory markers viz., caryophyllene oxide, octacosane, heneicosane, agarospirol, n-hexadecanoic acid, α-eudesmol, α-santalol and inoculum guided in-vitro agarwood production restoring the prized aroma, therapeutic efficacy, and wild population. Phytomedicinal uasge, biomarkers, immunomodulatory and related biological activities of Aquilaria malaccensis . • Critically endangered Aquilaria malaccensis Lam. is globally known for unique aroma. • High value agarwood oil is traditionally used as a phytomedicine in several chronic degenerative ailments. • Biomarkers exhibited pharmacological evaluation and in-silico immunomodulatory potential against SARS-CoV2. • Several genes WRKY, PAL, GLU were expressed during formation of agarwood as response to fungal infection, mechanical damage, and stress. • Futuristic scope on gene expression and marker-driven agarwood production with immunomodulatory potential.

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