OBJECTIVES:The incidence of cancer, a second leading cause of death globally, continues to rise steadily, and could reach 28.4 million cases by 2040, if no action is taken. Prostate cancer, the second most common cancer in men globally following lung cancer, accounted for 1,414,259 new cases and led to 375,304 deaths in 2022. Chemotherapy and surgery remain the major treatments however, they are associated with side effects. In this study, the anticancer potentials of ten (10) isoflavonoids from Millettia griffoniana Bail was explored. METHODS:Anti-cell growth (MTT), proliferative (CCK-8) and clonogenic effects of these isoflavonoids were investigated. Furthermore, the most potent compound (isojamaicin) was investigated for its potential to induce apoptosis, inhibit cell migration/invasion and cell adhesion. RESULTS:Out of the 10 isoflavonoids isolated from M. griffoniana, isojamaicin significantly inhibited PC3 and LNCaP cell growth and proliferation in a concentration dependent manner. It also significantly (p<0.001) inhibited PC3 cell clone formation. It induced a potent (near 40 %) increment of apoptotic cell population in PC3 cells at both 30 and 60 μg/mL; which was followed by a notable increase in caspase-3 activity. Isojamaicin induced potent inhibition of PC3 cell invasion/migration and increased adhesion of PC3 cells to the extracellular matrix (collagen). CONCLUSIONS:This study provides an unprecedented report of the anti-prostate cancer potential of isojamaicin and its possible underlying mechanisms. It merits further in vivo research to support the in vitro findings.

Pancreatic and colorectal cancer are two of the most lethal cancers; this stems from poor prognosis. Current treatments may lack effectiveness and produce dangerous side effects, hence a need for alternatives. Medicinal plants like Millettia griffoniana may possess anti-cancer properties. This study aimed to isolate and identify compounds from M. griffoniana to test for potential anti-cancer activity on pancreatic and colorectal cancer. Seeds and root bark of M. griffoniana underwent solvent extraction and separation using column chromatography. Isolated compounds were screened using AlamarBlue assays and cytotoxic compounds were identified with 2D NMR. Compounds were subject to cellular viability assays using AlamarBlue and xCELLigence analysis. The Caspase Glo®-3/7 kit measured caspase activity and Real-Time PCR analysis measured apoptosis-related gene expression. 7 compounds were isolated and screened. Compounds 5 and 7 were chosen; identified as durmillone and isojamaicin. Both showed varying concentration-dependent cytotoxic activity, in AlamarBlue and xCELLigence assays, for both cell lines. Caspases 3 and 7 were up-regulated and both compounds up-regulated BAX and down-regulated BCL-2 a nd p53 in both cell lines. Durmillone and isojamaicin displayed cytotoxic activity on pancreatic and colorectal cancer. Apoptotic activity induced by the compounds was verified by the up-regulation of caspase activity and BAX and down-regulation of BCL-2 and p53 . Further studies need to be done towards understanding the mechanisms by which these compounds bring about their cytotoxic activity.

Phytochemical study of Uvaria comperei afforded an alkaloid, 8,9-dimethoxy-5H-phenanthridin-6-one (1), isolated and characterised (assignment of 1H and 13C NMR) for the first time from a natural source along with two flavonoids, (2S)-5-hydroxy-7,8-dimethoxyflavanone (2) and (2S)-7-hydroxy-5-methoxy-6,8-dimethylflavone (3). Clethric acid (4), oleanoic acid (5), β-sitosterol 3-O-β-D-glucopyranoside (9), β-sitosterol palmitate (6) and a mixture of stigmasterol (7) and β-sitosterol (8) were isolated from Oxyanthus unilocularis. The structures of these compounds were elucidated using modern spectroscopic techniques including1D and 2D Nuclear Magnetic Resonance (NMR) Spectroscopy (1H, 13C, 1H-1H COSY, HSQC, HMBC) and Mass Spectrometry. Some fractions and compounds from Uvaria comperei exhibited good antifungal activity against clinical isolates and standard strains of yeast species of Candida and Cryptococcus genera while extracts from Oxyanthus unilocularis displayed weak antifungal activity. The results obtained show that Uvaria comperei could be a potential source of antifungal drugs.

BACKGROUND:Plants from garcinia genus have been used for centuries against several diseases.OBJECTIVE:This study aimed to investigate the mechanism of apoptosis induced by epigarcinol and isogarcinol isolated from the root of Garcinia ovalifolia (Clusiaceae) on human promyelocytic leukemia (HL-60 cells).METHODS:Epigarcinol and isogarcinol were isolated from the root of G. ovalifolia by using column chromatography method. The antiproliferative property of these molecules and fractions were assessed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The light fluorescence microscope was utilized to observe the morphological changes of HL-60 cells after 24 h treatment. Early apoptosis and cell cycle distribution were analyzed by using flow cytometry (FCM).RESULTS:The results showed that epigarcinol and isogarcinol inhibited the proliferation of HL-60 and PC-3 cells in a concentration-dependent manner with IC50 varying between 4 and 76 µg/mL depending on the cell line and the molecule. The apoptosis rate and the number of apoptotic cells significantly increased with the augmentation of the concentration of the molecules. The results of flow cytometry (FCM) indicated that epigarcinol and isogarcinol induced significant G2/S arrest of HL-60 cells, the disruption of mitochondrial membrane potential and reactive oxygen species (ROS) generation.CONCLUSION:These results indicated that epigarcinol and isogarcinol demonstrated in vitro antiproliferative properties and induce apoptosis of HL-60 cells which is related to the G2/S arrest, and it exerts its apoptotic effect through the loosing of mitochondrial membrane potential.

The β-D-galactopyranoside of the tetracosanoic acid ( 1 ) was isolated from the stem barks of Erythrina addisoniae along with known tetracosanoic acid ( 2 ), α-sophoradiol ( 3 ), stigmasterol ( 4 ), warangalone ( 5 ), 3- O β-D-glucopyranoside of β-sitosterol ( 6 ) and 7- O -β-D-glucopyranoside of daidzein ( 7 ). Two known compounds (erythrinasinate (8) and erycristagallin ( 9 )) were also isolated from the root barks of Erythrina mildbraedii . Their structures were assigned on the basis of spectroscopic data and chemical transformation. KEY WORDS : Erythrina addisoniae , Erythrina mildbraedii , Root barks, Stem barks, Leguminosae, Glucoside acid Bull. Chem. Soc. Ethiop. 2014 , 28(1), 155-159. DOI: http://dx.doi.org/10.4314/bcse.v28i1.19

Context: Millettia griffoniana Baill. (Fabaceae), which contains isoflavonoids like griffonianone C (Griff C), is commonly used in the folk medicine in Cameroon to treat various ailments. Possible health benefits of Griff C which include alleviation of menopausal symptoms, limitation of bone resorption, and lowering of the risks of cancer and cardiovascular diseases attracted our interest. Objective: The effects of Griff C on the regulation of the expression of proliferation markers such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CD1) and Ki-67 are investigated here. Its role in apoptosis or cell survival, through the phosphatidylinositol 3 kinase-Akt (PI3K-Akt) signaling pathway is further studied. Materials and methods: Semiquantitative real-time PCR was performed to analyze the effects of Griff C on gene expression in MCF-7 cells. Western blot analysis was used to assess the role of Griff C on the expression of phosphorylated Akt in MCF-7 cells. Results: Griff C induced a 4.84-fold increase in the expression of Ki-67 mRNA at the concentration of 10−8 M and a 3.90-fold increase of CD1 mRNA at 10−7 M. Griff C slightly increased the phosphorylation of Akt at its serine 473 residue. Akt phosphorylation was inhibited by the PI3K inhibitor, LY294002, but not by the specific estrogen receptor antagonist, fulvestrant. Discussion and conclusion: These findings suggest that Griff C can modulate proliferation of MCF-7 cells. Our results also suggest that Griff C can affect the PI3K-related signaling pathway. Thus, Griff C may exert part of its low proliferative and antiapoptotic effects by a nongenomic mode of action.

A new furanonaphthoquinone named 2-acetyl-6,7-dimethoxynaphtho[2,3-b]furan-4,9-quinone (1) was isolated from the stem bark of Millettia versicolor together with five known compounds (-sitosterol glucopyranoside, oleanolic acid, 2-acetylnaphtho[2,3-b]furan-4,9-quinone, 2-acetyl-6-methoxynaphtho[2,3-b]furan-4,9-quinone and 2-acetyl-7methoxynaphtho[2,3-b]furan-4,9-quinone). Four known compounds (lupeol, tetracosanoate of 1-glycerol, stigmasterol and 24-hydroxytetracosanoate of 1-glycerol) were also isolated from the stem bark of Millettia zechiana . The structure of compound ( 1) was elucidated based on 1D- and 2D-NMR and EIMS spectra.

Bridelia grandis is used in most parts of tropical Africa for the treatment of diabetes. The anti-diabetic properties of the methanolic stem bark extract of this plant was studied in ob/ob and db/db mice. The plant extract induced hypoglycaemic effects of long duration in the ob/ob mice, while its effects were less pronounced in the db/db mice. Twenty four hours after the cessation of drug administration, both ob/ob and db/db extract treated animals still had significantly lower fasting blood sugar levels when compared to controls, thus confirming its antidiabetic properties.

In the present study, we investigated whether griffonianone C (Griff C), extracted from root bark of Millettia griffoniana, changes the expression of several estrogen-responsive genes in the vena cava of ovariectomised rats. For this purpose, we subcutaneously administered Griff C (2, 10, or 20mg/kg/d BW), 17β-estradiol (E2: 10μg/kg/d BW) as positive control, and a vehicle control respectively for three days. Relative expression levels of estrogen receptor α (ERα), progesterone receptor (PR), cyclooxygenase2 (Cox-2), vascular endothelial growth factor (VEGF), VEGF-receptor 2, angiotensin converting enzyme (ACE), endothelial NO synthase (eNOS), proliferating cell nuclear antigen (PCNA) and Ki67 mRNA extracted from the vena cava of these rats were quantified by real-time PCR. Results showed that Griff C up-regulated the expression of PR, ACE, ERα, VEGF, VEGFR2 and Ki67. However, the results of Cox-2, PCNA, and eNOS expression did not reach significance in the E2 and Griff C treated samples. These results show that griffonianone C regulated a few of the analysed genes in a similar fashion than estradiol; however, others showed a different pattern. This suggests that some of the biological effects attributed to M. griffoniana are mediated via ER pathway others may be mediated via other pathways.

In most developing countries, 70–80% of the population still resort to traditional medicine for their primary health care. This medicine utilises medicinal plants which are traditionally taken as concoction and infusion. The root and stem bark of Millettia griffoniana (Leguminosae), has been reported to contain isoflavonoids, alkaloids, and diterpenoids. The possible benefit of some bioactive isoflavones derived from M. griffoniana prompted us to screen them for estrogenic activity. Six isoflavones and coumarin derived from M. griffoniana (bail) namely, compound nos. 1–6 (Fig. 1) were tested for their potential estrogenic activities in three different estrogen receptor alpha (ERα)-dependent assays. In a yeast-based ERα assay, all test substances and 17β-estradiol as endogenous agonist, showed a significant induction of β-galactosidase activity. The test compounds at the concentration of 5×10−6 M could achieve 59–121% of the β-galactosidase induction obtained with 10−8 M 17β-estradiol (100%). In the reporter gene assay based on stably transfected MCF-7 cells (MVLN cells), the estrogen responsive induction of luciferase was also stimulated by the M. griffoniana isoflavones. In Ishikawa cells, all substances exhibited estrogenic activity revealed by the induction of alkaline phosphatase (AlkP) activity. The estrogenic activities of isoflavones from M. griffoniana could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ERα. Although all substances showed estrogenic effects, 4′-methoxy-7-O-[(E)-3-methyl-7-hydroxymethyl-2,6-octadienyl]isoflavone (7-O-DHF), Griffonianone C (GRIF-C), and 3',4'-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone (7-O-GISO) were found to be the most potent of tested substances. In summary, estrogenic activities of the isoflavones derived from M. griffoniana were described for the first time using reporter gene assays and the estrogen-inducible AlkP Ishikawa model.

Three new isoflavonoids, griffonianone F, G and H were isolated from the seeds of Millettia griffoniana, along with the known prebarbigerone, pseudobaptigenin, pseudobaptigenin methyl ether, tephrosin, dipterixine, odorantine, 7,4',5'-tetramethoxyisoflavone and isojamaicin. Their structures were assigned on the basis of spectroscopic data and chemical transformations.

Two new prenylated isoflavonoids, namely 7-methoxyebenosin and griffonianone E along with the known calopogonium isoflavone B and 7,2'-dimethoxy-4',5'-methylenedioxy isoflavone were isolated from the seeds of Millettia griffoniana. Their structures were assigned on the basis of spectroscopic data. The new compounds exhibit moderate trypanocidal and antiplasmodial activities.

A new isoflavone, griffonianone D (1), and the previously known compounds durmillone and odorantin were isolated from a chloroform extract of the root bark of Millettia griffoniana. The structure of 1 was established as (7E)-(6",7"-dihydroxy-3",7"-dimethyloct-2"-enyl)oxy-4'-methoxyisoflavone on the basis of its spectral data. The chloroform extract of the root bark of M. griffoniana and compound 1 showed anti-inflammatory effects in different experimental models of inflammation.

The dichloromethane-soluble fraction of the methanol extract of the stem bark of Millettia versicolor Welw. (Leguminosae) has been shown to possess anti-inflammatory activity. The chromatographic fractionation and subsequent analysis of the spectroscopic data of this extract led to the isolation and identification of 2-acetyl-7-methoxynaphtho[2,3- b]furan-4,9-quinone (1) along with two known quinones. Pharmacological data demonstrate that compound 1 has relevant anti-inflammatory properties whereas the other two isolated compounds do not.

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Three new isoflavonoids, griffonianone A (1), B (2) and C (1, Fig. 1) were isolated from the root bark of Millettia griffoniana, along with the known maximaisoflavone G (5) and 7-hydroxy-6-methoxy-3′,4′-methylenedioxyisoflavone (6). Their structures were assigned on the basis of spectroscopic data and chemical transformations.

The stein bark and seeds of Staudtia kamerunensis have been investigated for the first ri,ne. Front the hexane extract of the seeds, glycerol tritetradecanoate (trimyristin, glycerol trimyristate) and six lignans were isolated These lignans are: otobain, hydroxyotobain, otobaphenol, licarin A, licarin B and (-) dihydroxyguaiaretic acid The ethyl acetate extract of the stem bark gave a seventh lignan, otobuene.

Root bark of Millettia griffoniana yielded two new O-geranylated isoflavones and a new 3-phenylcoumarin. Their structures were determined on the basis of spectral evidence as 4′-methoxy-7-O-[(E)-3-methyl-7-hydroxymethyl-2,6-octadienyl]isoflavone, 3′,4′-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone and 4-hydroxy-5,6,7-trimethoxy-3-(3′,4′-methylenedioxy)phenylcoumarin.

A new O-geranylated isoflavone, 3′,4′-methylenedioxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl] isoflavone, 7-O-geranylpseudobaptigenin, was isolated in addition to seven other known compounds from the root bark of Millettia griffoniana. The structure of the new compound was elucidated on the basis of spectroscopic data.