Abstract:
The rhizome of Helminthostachys zeylanica, referred to as 'Daodi-Ugon' or 'Ding-Di-U-Gon,'
possesses a rich historical background in traditional Chinese medicine, demonstrating efficacy in
the treatment of diverse conditions such as malaria, dysentery, fever, burns, hepatic disorders, and
pneumonia (including catarrh and early stages of phthisis). This indigenous fern, a member of the
Ophioglossaceae family, is endemic to southeastern Asia. Our investigation led to the
identification of more than 20 novel bioactive compounds from this traditional Chinese medicine
(TCM) herb. In the commercial sphere, two distinct products derived from H. zeylanica, namely
Hei Daodi-Ugon (HZB) and Hong Daodi-Ugon (HZR), are available. Empirical evidence from
seasoned TCM practitioners suggests that HZR surpasses HZB in terms of both quality and
efficacy. Intriguingly, preliminary anti-inflammatory screenings revealed that the aqueous layer
of HZR exhibited superior activity in reducing the levels of IL-1β, iNOS, and COX-2 compared to
the corresponding layer in HZB. Conversely, the ethyl-acetate layer of HZB demonstrated stronger
activity than its HZR counterpart, despite a prior report indicating no significant difference in the
composition of HZR and HZB based on the total content of the three standard organic compounds
(ugonins J and M and quercetin) using conventional UV-Vis HPLC analysis. Our findings align with
the observations of TCM practitioners, particularly given the prevalent practice of preparing TCM
formulations with boiling water. In this context, we present an evidence-based analysis
elucidating the chemical distinctions between Hei Daodi-Ugon (HZB) and Hong Daodi-Ugon
(HZR) utilizing GNPS molecular network analysis and subsequent LC quantification of flavonoid
glycosides in both water-soluble HZR and HZB extracts. Furthermore, our exploration of
additional medical applications of HZ components and extracts revealed promising outcomes.
Based on in vivo data demonstrating an increase in serum amino-terminal propeptide of type 1
procollagen (PINP) levels and a reduction in radiographic healing time (RHT) through oral
administration of HZ for 42 days, we propose the potential use of HZ in treating patients with
ankle fractures requiring surgical intervention. Additionally, our findings suggest that ugonin L
holds promise as a candidate for the development of novel anti-resorption therapies. Moreover,
ugonin P emerged as a potential candidate for the development of therapeutic agents targeting
lung cancer.
