Antidiabetic and Cytotoxic Activities of Rotenoids and Isoflavonoids Isolated from Millettia pachycarpa Benth

Abstract

A phytochemical investigation of the root and leaf extracts of Millettia pachycarpa Benth resulted in the isolation and identification of 16 compounds, including six rotenoids ( 1 – 6 ) and 10 prenylated isoflavonoids ( 7 – 16 ). Compound 4 was isolated as a scalemic mixture, which was resolved by chiral HPLC to afford (−)-(6a S ,12a S )-12a-hydroxy-α-toxicarol ( 4 ) and (+)–(6a R ,12a R )-12a-hydroxy-α-toxicarol ( 4 ). (+)-(6a R ,12a R )-Millettiapachycarpin ( 3 ) and (−)-(6a S ,12a S )-12a-hydroxy-α-toxicarol ( 4 ) were isolated as new compounds. The absolute configuration of (−)-(6 R )-pachycarotenoid ( 2 ), (+)–(6a R ,12a R )-millettiapachycarpin ( 3 ), (−)-(6a S ,12a S )- 4 and (+)–(6a R ,12a R )-12a-hydroxy-α-toxicarol ( 4 ), (+)-(6a S ,12a S )-( 5 ), and (−)-(6a S ,12a S ,2″ R )-sumatrol ( 6 ) were identified by electronic circular dichroism (ECD) data. (−)-(6a S ,12a S ,2″ R )-Sumatrol ( 6 ) was also confirmed by X-ray diffraction analysis using Cu–Kα radiation. Antidiabetic activities, including α-glucosidase and α-amylase inhibitory activities, and cytotoxicities against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells of some isolated compounds were evaluated. Of these, isolupalbigenin ( 11 ) exhibited the highest α-glucosidase inhibitory activity, with an IC 50 value of 11.3 ± 0.2 μM, whereas the scalemic mixture of 12a-hydroxy-α-toxicarol ( 4 ) displayed the best α-amylase inhibitory activity, with an IC 50 value of 106.9 ± 0.2 μM. Euchrenone b10 ( 15 ) exhibited the highest cytotoxicity against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells, with IC 50 values of 40.3, 39.1, and 15.1 μM, respectively. In addition, molecular docking simulations of α-glucosidase inhibition of the active compounds were studied.

The effects of flavonoids in experimental sepsis: A systematic review and meta‐analysis

“…Sulfated flavonoids can present themselves as single‐ or multi‐sulfate esters, while rotonoid isoflavonoids are chemically biosynthesized from isoflavones and are characterized by a four‐ring chromanochromanone structure (Dixon, 1999) (Figure 2). Studies have described their anti‐inflammatory, antioxidant, antitumor, antimicrobial properties (Habbu et al, 2009; Ren et al, 2017; Teles et al, 2018), antidiabetic, and cytotoxic properties (Suthiphasilp et al, 2022). Treatment with the sulfated flavonoid persicarin (Per) (25), improved the survival rate and life expectancy of animals with sepsis (Kim et al, 2013).…”

Uncommon Millettia pachycarpa Benth poisoning: A case report

“…While both plants belong to the Fabaceae family, they exhibit marked differences in leaf and fruit morphology; notably, the fruit of M. pachycarpa Benth is large and plump, resembling an egg, whereas the fruit of S. suberectus Dunn is narrow and elongated, akin to a sickle. In traditional Chinese medicine, their pharmacological applications are different, with the former primarily used as an insecticide, [2] while the latter is known to promote blood circulation. [7] From laboratory examinations, distinctive characteristics of such poisonings can be discerned, notably an aberrant arterial blood gas profile: isolated carbon dioxide retention without hypoxemia, significantly reduced pH, and marked elevation in lactate levels.…”

“…While both plants belong to the Fabaceae family, they exhibit marked differences in leaf and fruit morphology; notably, the fruit of M. pachycarpa Benth is large and plump, resembling an egg, whereas the fruit of S. suberectus Dunn is narrow and elongated, akin to a sickle. In traditional Chinese medicine, their pharmacological applications are vastly different, with the former primarily used as an insecticide, [ 2 ] while the latter is known to promote blood circulation. [ 7 ]…”

“…Various toxic compounds, including rotenone and its analogs, can be isolated from the fruits and rhizomes of M. pachycarpa Benth. [ 2 ] Rotenone is widely regarded as the main culprit of the toxic symptoms; as a lipophilic compound, it traverses biological membranes, including the blood–brain barrier, and directly affects cells by inhibiting the mitochondrial complex I of the electron transport chain. [ 3 ] This action decreases adenosine triphosphate (ATP) formation, leading to cell death.…”

Mechanisms analysis for Formononetin counteracted‐Osimertinib resistance in non‐small cell lung cancer cells: From the insight into the gene transcriptional level

“…Formononetin belongs to the isoflavones and is mainly found in leguminous plants such as the roots of astragalus (Yang et al., 2014). Numerous studies have shown that isoflavonoids compounds possessed various potentials against tumor growth (Aiello et al., 2021; Stojkovic et al., 2020; Suthiphasilp et al., 2022). In recent years, researchers have done a lot of work on the pharmacological effects of Formononetin, showing that it has anti‐inflammatory, antioxidant, anti‐apoptotic, lipid‐modulating, antithrombotic, and tumor inhibition effects (Machado Dutra et al., 2021).…”