Abstract
Picroside-II (P-II), an iridoid glycoside, is used as an active ingredient of various commercial herbal formulations available for the treatment of liver ailments. Despite this, the knowledge of P-II biosynthesis remains scarce owing to its negligence in Picrorhiza kurroa shoots which sets constant barrier for function validation experiments. In this study, we utilized natural variation for P-II content in stolon tissues of different P. kurroa accessions and deciphered its metabolic route by integrating metabolomics of intermediates with differential NGS transcriptomes. Upon navigating through high vs. low P-II content accessions (1.3–2.6%), we have established that P-II is biosynthesized via degradation of ferulic acid (FA) to produce vanillic acid (VA) which acts as its immediate biosynthetic precursor. Moreover, the FA treatment in vitro at 150 μM concentration provided further confirmation with 2-fold rise in VA content. Interestingly, the cross-talk between different compartments of P. kurroa, i.e., shoots and stolons, resolved spatial complexity of P-II biosynthesis and consequently speculated the burgeoning necessity to bridge gap between VA and P-II production in P. kurroa shoots. This work thus, offers a forward looking strategy to produce both P-I and P-II in shoot cultures, a step toward providing a sustainable production platform for these medicinal compounds via-à-vis relieving pressure from natural habitat of P. kurroa.
Highlights
Picrorhiza kurroa, locally named as Kutki, is a high altitude (3000–5000 m) medicinal herb distributed in the North-Western Himalayas of India
The metabolic network of picrosides production is overwhelmingly complex as multiple pathways contribute to their biosynthesis in P. kurroa
To investigate the metabolic basis of P-II biosynthesis, we have employed a strategy utilizing natural genetic diversity existing for the production of P-II among P. kurroa accessions collected from different geographic locations of North-Western Himalayas, India
Summary
Picrorhiza kurroa, locally named as Kutki, is a high altitude (3000–5000 m) medicinal herb distributed in the North-Western Himalayas of India. It is used for the treatment of various ailments due to pharmacological properties like hepatoprotective, antiallergic, antiasthmatic, antioxidant, anticancerous, and immunomodulatory and provide livelihood and health security to a large segment of high altitude populations (Kumar et al, 2015a, 2017). Modular Design of Picroside-II Biosynthesis in P. kurroa medicinal herb. It originates as a young bud on stolons which develops to produce mature stolon and subsequently rhizomes with self-governing roots and shoots compartments (Pandit et al, 2013a). The scarcity of herbal raw material caused economic constraints on local communities and resulted in adulteration of P. kurroa, thereby affecting quality and efficacy of drugs due to lower levels of picroside-I (P-I) and picroside-II (P-II), the signature bioactive compounds of P. kurroa (Shitiz et al, 2013)
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