Mechanism & inhibition kinetics of bioassay-guided fractions of Indian medicinal plants and foods as ACE inhibitors

Abstract

Hypertension is a becoming a major threat to the world. Angiotensin converting enzyme (ACE) is a key part in the renin angiotensin aldosterone system (RAAS) which control blood pressure. Over expression of RAAS is related with vascular hypertension, ACE inhibition has turned into a noteworthy target for controlling hypertension. In the search of lead molecules from plant origin as a substitute for toxic synthetic drugs, 25 Indian medicinal plants and foods were screened for their ACE inhibitory activity. IC50 (50% inhibition of ACE) values of hydroalcoholic crude extracts and fraction were determined by a colorimetric method. Active fractions were further screened to determine the enzyme kinetics, mode, specificity and mechanism of inhibition. Standardization was done by determining total phenolics and flavonoids as gallic acid and quercetin equivalents/mg of extract respectively. Among 25 crude extracts, Cynara scolymus extract showed the best activity, IC50 value 356.62 μg/mL. ACE inhibition resulting from protein precipitation was highest in Coscinium fenestratum. Lineweaver-Burk plots revealed a competitive mode of inhibition for Punica granatum ethyl acetate fraction. Fractions of Cassia occidentalis, Cynara scolymus and Embelia ribes were found to be non-specific inhibitors of ACE. Embelia ribes, Cassia occidentalis and Coscinium fenestratum fractions inhibited the ACE by Zn2+ ion chelation. Research revealed the potential of tested plants fractions as ACE inhibitors along with their inhibition kinetics and mechanism of inhibition. These active plant fractions might find importance in the development of potential antihypertensive agents after further investigations using preclinical and clinical trials.

Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus

“…ref. [74]). Many compounds studied in works referenced in Section 4.7 were plant extracts, derivatives, or analogues.…”

COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance

“…A number of ideas and principles, borrowed in established and recent design of synthetic vaccines and petidomimetics, were used (see ref [3] for discussion and e.g. refs [63][64][65][66][67][68][69]), as well as some of the ideas that lie behind the popular ZINC data base [70]. As discussed in refs [3,4], the present investigation started as a use case for the Hyperbolic Dirac Net (HDN) and particularly the associated Q-UEL language for automated inference [34][35][36][37].…”

“…In an automated approach such as that favored by Q-UEL, a variable (such as a Perl variable $mol) to ZINC00011032 and is set an the Q-UEL application goes to http://zinc15.docking.org/substances/search/?q=$mol. Any references to experimental binding results concern data from cited papers, and see for example ref [69] for typical methods used for natural herbal compounds. As discussed in ref [3], Q-UEL helped gather these in the form of Q-UEL knowledge representation tags, so they become part of the growing knowledge Representation store.…”

“…In Fig. 6 is shown a set of compounds from the ZINC data base [69], and most were identified from the original 11β-hydroxysteroid dehydrogenase type 1 study [50] and subsequent studies. These bind significantly by usual criteria, but more weakly.…”

Combating COVID-19: The role of drug repurposing and medicinal plants

“…Various research studies focusing on plant species such as Coriandrum sativum, Coscinium fenestratum, Cynara scolymus, Punica granatum and Cassia occidentalis have demonstrated them to inhibit the virus entry significantly via ACE inhibition A lot of research trials has been conducted regarding ACE inhibition thus locking virus entry [ 78 , 102 ]. Some plants like Ocimum sanctum (Holy basil)) Solanum nigrum ( Black nightshade ) and Vitex negundo (Chinese chaste tree) possess anti-reverse transcriptase activity of HIV could also be used for the screening and development of COVID-19 drug [ 103 ].…”