Pierre Mkounga | University of Yaounde I (original) (raw)

Papers by Pierre Mkounga

According to some recent studies, Cameroon is one of the sub-Saharan African countries most affec... more According to some recent studies, Cameroon is one of the sub-Saharan African countries most affected by hepatitis C, with low access to the standard therapy based on the combination of pegylated interferon and ribavirin. A first ethnobotanical survey, conducted in the Western region of Cameroon, reported the use of several medicinal plants in traditional medicine for the healing of liver-related disorders. Crude organic extracts of five plants surveyed were prepared and their effect against hepatitis C virus (HCV) infection investigated. The HCV JFH1 strain cell culture system HCVcc was used. The antiviral activity was quantified by immunofluorescent labeling of HCV E1 envelope protein at 30 h post-infection in the presence of the plant extracts. Active compounds were then tested in time course infection experiments. Dose-response and cellular toxicity assays were also determined. Three extracts, methanol extracts from roots of Trichilia dregeana, stems of Detarium microcarpum and leaves of Phragmanthera capitata, showed anti-HCV activity, with half-maximal inhibitory concentration of 16.16, 1.42, and 13.17 μg/mL, respectively. Huh-7 cells were incubated with the extracts for 72 h and it appears that T. dregeana extract is not toxic up to 200 μg/mL, D. microcarpum up to 100 μg/mL and P. capitata up to 800 μg/mL. All the three extracts showed a strong inhibition of HCV entry and no effect on replication or secretion. Taken together, these results showed that extracts from Cameroonian medicinal plants are promising sources of anti-HCV agents.

Three new limonoids, rubescins A–C (1–3), and three known compounds including, havanensin type li... more Three new limonoids, rubescins A–C (1–3), and three known compounds including, havanensin type limonoid TS3 (4), β-sitosterol, and stigmasterol were isolated from the root bark of Trichilia rubescens. Their structures were elucidated by means of extensive spectroscopic analyses, particularly one dimensional (1D)-and 2D-NMR techniques in conjunction with mass spectrometry. Rubescins A–C (1–3) and limonoid TS3 (4) were evaluated for their protective effects against oxidative stress induced in HC-04 cells by H 2 O 2. Compound (1) showed strong inhibitory effects on lactase dehydrogenase (LDH) leakage, being as active (IC 50 value of 0.0026 µM) as the positive control quercetin (IC 50 value of 0.0030 µM).

Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Centra... more Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Central Africa regions to treat liver diseases. Antiviral properties of this plant were reported against Hepatitis B virus, while effects against Hepatitis C virus (HCV) remained unknown. This study reports for the first time, the effects of Ea crude extract and fractions on HCV replication. Furthermore, the effect of one Ea fraction on the transcriptional expression of two interferon-stimulated genes (ISGs) was also investigated. A methylene chloride–methanol (MCM) stem bark crude extract and different MCM fractions (EaF0, EaF5, EaF10, EaF25, and EaF100) were prepared and tested on LucUbiNeo-ET and Huh 5.15 cells lines used as genotype 1b (GT1b) replicon systems. The cells were incubated with crude extract and fractions at various concentrations. Then, the antiviral activity was assessed by luciferase reporter assay and the cell viability by MTT assay. Gene expression was also analyzed using quantitative real time RT-PCR. Results showed that the Ea crude extract dose-dependently inhibited HCV replication after 24 and 72 h of incubation. The MCM fraction (EaF10) exhibited the strongest anti-HCV properties with an IC 50 ¼ 0:453 AE 0.00117 mg/ml and no reduction of cell viability at antiviral concentrations. This fraction also significantly induced the expression of heme oxygenase-1 (HO-1) (5.36-fold), and 2 0-5 0 oligoadenylate synthetase-3 (OAS-3) by 4.46-fold after 6 h and 2.31-fold after 24 h at the mRNA levels. Taken altogether, these results suggest that Ea may contain ingredients that indirectly regulate HCV replication.

In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on th... more In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 lg/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 lM daclatasvir or 1 lM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1 0-(oxy-diethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1-phenyl (2), and 6-phenyl, 4-(1 0-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle.

According to some recent studies, Cameroon is one of the sub-Saharan African countries most affec... more According to some recent studies, Cameroon is one of the sub-Saharan African countries most affected by hepatitis C, with low access to the standard therapy based on the combination of pegylated interferon and ribavirin. A first ethnobotanical survey, conducted in the Western region of Cameroon, reported the use of several medicinal plants in traditional medicine for the healing of liver-related disorders. Crude organic extracts of five plants surveyed were prepared and their effect against hepatitis C virus (HCV) infection investigated. The HCV JFH1 strain cell culture systemHCVcc was used. The antiviral activity was quantified by immunofluorescent labeling of HCV E1 envelope protein at 30 h post-infection in the presence of the plant extracts. Active compounds were then tested in time course infection experiments. Dose-response and cellular toxicity assays were also determined. Three extracts, methanol extracts from roots of Trichilia dregeana,stems of Detarium microcarpum and leaves of Phragmanthera capitata, showed anti-HCV activity, with half-maximal inhibitory concentration of 16.16, 1.42, and 13.17 µg/mL, respectively. Huh-7 cells were incubatedwith the extracts for 72 h and it appears that T. dregeana extract is not toxic up to 200 µg/mL, D. microcarpum up to 100 µg/mL and P. capitata up to 800 µg/mL. All the three extracts showed a strong inhibition of HCV entry and no effect on replication or secretion. Taken together, these results showed that extracts from Cameroonian medicinal plants are promising sources of anti-HCV agents

Chemical and Pharmaceutical Bulletin, 2013

Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type li... more Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type limonoid TS3 (4), β-sitosterol, and stigmasterol were isolated from the root bark of Trichilia rubescens. Their structures were elucidated by means of extensive spectroscopic analyses, particularly one dimensional (1D)- and 2D-NMR techniques in conjunction with mass spectrometry. Rubescins A-C (1-3) and limonoid TS3 (4) were evaluated for their protective effects against oxidative stress induced in HC-04 cells by H2O2. Compound (1) showed strong inhibitory effects on lactase dehydrogenase (LDH) leakage, being as active (IC50 value of 0.0026 µM) as the positive control quercetin (IC50 value of 0.0030 µM).

Archives of Virology, 2016

In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on th... more In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 µg/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 µM daclatasvir or 1 µM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1'-(oxydiethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1-phenyl (2), and 6-phenyl, 4-(1'-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle.

Biological Research, 2015

Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the ... more Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC. Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 μg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 μg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 μg/mL for (1), 34.15 μg/mL for (2) and 45.66 μg/mL for (3), compared to galantamine (IC50 of 8.22 μg/mL) used as positive control. The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.

Natural product communications, 2009

Bioassay-guided fractionation of the stem bark of Symphonia globulifera has yielded three known x... more Bioassay-guided fractionation of the stem bark of Symphonia globulifera has yielded three known xanthones, ugaxanthone (1), mbarraxanthone (2) and gentisein (3), two biflavonoid derivatives named GB2 (4) and manniflavanone GB3 (5), and one new polyoxygenated xanthone with an isoprenoid group, named globulixanthone F (6). The structures of these compounds were elucidated by means of spectroscopic methods. The spectral data of 1 and 2 are reported here for the first time, as well as the antimicrobial activity of globulixanthone F against a range of microorganisms. We also report the total synthesis of the xanthone skeleton.

The Natural Products Journal, 2013

Frontiers in Microbiology, 2015

According to some recent studies, Cameroon is one of the sub-Saharan African countries most affec... more According to some recent studies, Cameroon is one of the sub-Saharan African countries most affected by hepatitis C, with low access to the standard therapy based on the combination of pegylated interferon and ribavirin. A first ethnobotanical survey, conducted in the Western region of Cameroon, reported the use of several medicinal plants in traditional medicine for the healing of liver-related disorders. Crude organic extracts of five plants surveyed were prepared and their effect against hepatitis C virus (HCV) infection investigated. The HCV JFH1 strain cell culture system HCVcc was used. The antiviral activity was quantified by immunofluorescent labeling of HCV E1 envelope protein at 30 h post-infection in the presence of the plant extracts. Active compounds were then tested in time course infection experiments. Dose-response and cellular toxicity assays were also determined. Three extracts, methanol extracts from roots of Trichilia dregeana, stems of Detarium microcarpum and leaves of Phragmanthera capitata, showed anti-HCV activity, with half-maximal inhibitory concentration of 16.16, 1.42, and 13.17 μg/mL, respectively. Huh-7 cells were incubated with the extracts for 72 h and it appears that T. dregeana extract is not toxic up to 200 μg/mL, D. microcarpum up to 100 μg/mL and P. capitata up to 800 μg/mL. All the three extracts showed a strong inhibition of HCV entry and no effect on replication or secretion. Taken together, these results showed that extracts from Cameroonian medicinal plants are promising sources of anti-HCV agents.

The American journal of Chinese medicine, 2014

Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Centra... more Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Central Africa regions to treat liver diseases. Antiviral properties of this plant were reported against Hepatitis B virus, while effects against Hepatitis C virus (HCV) remained unknown. This study reports for the first time, the effects of Ea crude extract and fractions on HCV replication. Furthermore, the effect of one Ea fraction on the transcriptional expression of two interferon-stimulated genes (ISGs) was also investigated. A methylene chloride-methanol (MCM) stem bark crude extract and different MCM fractions (EaF0, EaF5, EaF10, EaF25, and EaF100) were prepared and tested on LucUbiNeo-ET and Huh 5.15 cells lines used as genotype 1b (GT1b) replicon systems. The cells were incubated with crude extract and fractions at various concentrations. Then, the antiviral activity was assessed by luciferase reporter assay and the cell viability by MTT assay. Gene expression was also analyzed using ...

Two prenylated xanthone derivatives, named globulixanthones C and D and one bis-xanthone, designa... more Two prenylated xanthone derivatives, named globulixanthones C and D and one bis-xanthone, designated globulixanthone E, have been isolated from the root bark of Symphonia globulifera. The structures of these compounds were elucidated by a detailed spectroscopic analysis. They have been shown to exhibit in vitro significant antimicrobial activity against a range of micro-organisms.

ChemInform, 2014

Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type li... more Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type limonoid TS3 (4), β-sitosterol, and stigmasterol were isolated from the root bark of Trichilia rubescens. Their structures were elucidated by means of extensive spectroscopic analyses, particularly one dimensional (1D)and 2D-NMR techniques in conjunction with mass spectrometry. Rubescins A-C (1-3) and limonoid TS3 (4) were evaluated for their protective effects against oxidative stress induced in HC-04 cells by H 2 O 2 . Compound (1) showed strong inhibitory effects on lactase dehydrogenase (LDH) leakage, being as active (IC 50 value of 0.0026 µM) as the positive control quercetin (IC 50 value of 0.0030 µM).

ChemInform, 2010

Species. -The title compounds (I) and (II) show significant antimicrobial activities against a wi... more Species. -The title compounds (I) and (II) show significant antimicrobial activities against a wide range of bacteria and fungi. -(TSAFFACK, M.; NGUEMEVING, J. R.; KUETE, V.; TCHIZE, B. L. S. N.; MKOUNGA, P.; BENG, V. P.; HULTIN, P. G.; TSAMO, E.; NKENGFACK*, A. E.; Chem.

Natural Product Research, 2011

This study was designed at evaluating the antimycobacterial, antibacterial and antifungal activit... more This study was designed at evaluating the antimycobacterial, antibacterial and antifungal activities of the CH2Cl2-CH3OH (1:1) extracts and isolated compounds, namely 3,4-dimethoxy-3',4'-methylenedioxy-7,7'-epoxylignan (1), genkwainin (2), pycnanthulignene C (3), 4,5-dimethoxy-3',4'-methylenedioxy-2,7'-cycloligna-7,7'-diene (4), pycnanthulignene A (5) from the roots, and calycosin (6), biochanin A (7) and prunetin (8), from the fruits of Pycnanthus angolensis. The microplate alamar blue assay and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration of the samples. The H+-ATPase-mediated proton pumping assay was used to evaluate one of the possible mechanisms of action of the extracts and isolated compounds. The results of MIC determinations showed that the extract from roots was able to prevent the growth of all the studied organisms, including mycobacteria, fungi, and Gram-positive and Gram-negative bacteria. All tested compounds showed antimicrobial activities to different extents, compound 1 and 8 exhibiting the best antimicrobial spectrum, with 92.3% of the tested organisms being sensitive. The results obtained in this study also showed that the extracts as well as most of the compounds were able to inhibit the H(+)-ATPase activity. The overall results provided evidence that P. angolensis and some of its components might be potential sources of antimicrobial drugs against tuberculosis, bacterial and fungal diseases.

Journal of Natural Products, 2002

Bioassay-guided fractionation of a root bark extract of Symphonia globulifera has yielded, in add... more Bioassay-guided fractionation of a root bark extract of Symphonia globulifera has yielded, in addition to stigmasterol, two new xanthones with isoprenoid units, named globulixanthones A (1) and B (2). The structures of these compounds have been elucidated by spectroscopic means. They possess significant cytotoxicity in vitro against the KB cell line.

CHEMICAL & PHARMACEUTICAL BULLETIN, 2010

Three new olean-12-ene derivatives (1-3), together with known urs-12-ene-3beta, 28-diol (4) were ... more Three new olean-12-ene derivatives (1-3), together with known urs-12-ene-3beta, 28-diol (4) were isolated from the stem root of Cylicodiscus gabunensis. The structures of the new compounds were established by chemical and spectroscopic means as beta-amyrin-n-nonyl ether (1), 22alpha-hydroxyolean-12-en-3beta-yl-beta-D-galactopyranoside (2), and 24-hydroxyolean-12-en-3beta-yl-beta-D-glucopyranoside (3).

According to some recent studies, Cameroon is one of the sub-Saharan African countries most affec... more According to some recent studies, Cameroon is one of the sub-Saharan African countries most affected by hepatitis C, with low access to the standard therapy based on the combination of pegylated interferon and ribavirin. A first ethnobotanical survey, conducted in the Western region of Cameroon, reported the use of several medicinal plants in traditional medicine for the healing of liver-related disorders. Crude organic extracts of five plants surveyed were prepared and their effect against hepatitis C virus (HCV) infection investigated. The HCV JFH1 strain cell culture system HCVcc was used. The antiviral activity was quantified by immunofluorescent labeling of HCV E1 envelope protein at 30 h post-infection in the presence of the plant extracts. Active compounds were then tested in time course infection experiments. Dose-response and cellular toxicity assays were also determined. Three extracts, methanol extracts from roots of Trichilia dregeana, stems of Detarium microcarpum and leaves of Phragmanthera capitata, showed anti-HCV activity, with half-maximal inhibitory concentration of 16.16, 1.42, and 13.17 μg/mL, respectively. Huh-7 cells were incubated with the extracts for 72 h and it appears that T. dregeana extract is not toxic up to 200 μg/mL, D. microcarpum up to 100 μg/mL and P. capitata up to 800 μg/mL. All the three extracts showed a strong inhibition of HCV entry and no effect on replication or secretion. Taken together, these results showed that extracts from Cameroonian medicinal plants are promising sources of anti-HCV agents.

Three new limonoids, rubescins A–C (1–3), and three known compounds including, havanensin type li... more Three new limonoids, rubescins A–C (1–3), and three known compounds including, havanensin type limonoid TS3 (4), β-sitosterol, and stigmasterol were isolated from the root bark of Trichilia rubescens. Their structures were elucidated by means of extensive spectroscopic analyses, particularly one dimensional (1D)-and 2D-NMR techniques in conjunction with mass spectrometry. Rubescins A–C (1–3) and limonoid TS3 (4) were evaluated for their protective effects against oxidative stress induced in HC-04 cells by H 2 O 2. Compound (1) showed strong inhibitory effects on lactase dehydrogenase (LDH) leakage, being as active (IC 50 value of 0.0026 µM) as the positive control quercetin (IC 50 value of 0.0030 µM).

Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Centra... more Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Central Africa regions to treat liver diseases. Antiviral properties of this plant were reported against Hepatitis B virus, while effects against Hepatitis C virus (HCV) remained unknown. This study reports for the first time, the effects of Ea crude extract and fractions on HCV replication. Furthermore, the effect of one Ea fraction on the transcriptional expression of two interferon-stimulated genes (ISGs) was also investigated. A methylene chloride–methanol (MCM) stem bark crude extract and different MCM fractions (EaF0, EaF5, EaF10, EaF25, and EaF100) were prepared and tested on LucUbiNeo-ET and Huh 5.15 cells lines used as genotype 1b (GT1b) replicon systems. The cells were incubated with crude extract and fractions at various concentrations. Then, the antiviral activity was assessed by luciferase reporter assay and the cell viability by MTT assay. Gene expression was also analyzed using quantitative real time RT-PCR. Results showed that the Ea crude extract dose-dependently inhibited HCV replication after 24 and 72 h of incubation. The MCM fraction (EaF10) exhibited the strongest anti-HCV properties with an IC 50 ¼ 0:453 AE 0.00117 mg/ml and no reduction of cell viability at antiviral concentrations. This fraction also significantly induced the expression of heme oxygenase-1 (HO-1) (5.36-fold), and 2 0-5 0 oligoadenylate synthetase-3 (OAS-3) by 4.46-fold after 6 h and 2.31-fold after 24 h at the mRNA levels. Taken altogether, these results suggest that Ea may contain ingredients that indirectly regulate HCV replication.

In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on th... more In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 lg/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 lM daclatasvir or 1 lM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1 0-(oxy-diethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1-phenyl (2), and 6-phenyl, 4-(1 0-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle.

According to some recent studies, Cameroon is one of the sub-Saharan African countries most affec... more According to some recent studies, Cameroon is one of the sub-Saharan African countries most affected by hepatitis C, with low access to the standard therapy based on the combination of pegylated interferon and ribavirin. A first ethnobotanical survey, conducted in the Western region of Cameroon, reported the use of several medicinal plants in traditional medicine for the healing of liver-related disorders. Crude organic extracts of five plants surveyed were prepared and their effect against hepatitis C virus (HCV) infection investigated. The HCV JFH1 strain cell culture systemHCVcc was used. The antiviral activity was quantified by immunofluorescent labeling of HCV E1 envelope protein at 30 h post-infection in the presence of the plant extracts. Active compounds were then tested in time course infection experiments. Dose-response and cellular toxicity assays were also determined. Three extracts, methanol extracts from roots of Trichilia dregeana,stems of Detarium microcarpum and leaves of Phragmanthera capitata, showed anti-HCV activity, with half-maximal inhibitory concentration of 16.16, 1.42, and 13.17 µg/mL, respectively. Huh-7 cells were incubatedwith the extracts for 72 h and it appears that T. dregeana extract is not toxic up to 200 µg/mL, D. microcarpum up to 100 µg/mL and P. capitata up to 800 µg/mL. All the three extracts showed a strong inhibition of HCV entry and no effect on replication or secretion. Taken together, these results showed that extracts from Cameroonian medicinal plants are promising sources of anti-HCV agents

Chemical and Pharmaceutical Bulletin, 2013

Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type li... more Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type limonoid TS3 (4), β-sitosterol, and stigmasterol were isolated from the root bark of Trichilia rubescens. Their structures were elucidated by means of extensive spectroscopic analyses, particularly one dimensional (1D)- and 2D-NMR techniques in conjunction with mass spectrometry. Rubescins A-C (1-3) and limonoid TS3 (4) were evaluated for their protective effects against oxidative stress induced in HC-04 cells by H2O2. Compound (1) showed strong inhibitory effects on lactase dehydrogenase (LDH) leakage, being as active (IC50 value of 0.0026 µM) as the positive control quercetin (IC50 value of 0.0030 µM).

Archives of Virology, 2016

In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on th... more In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 µg/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 µM daclatasvir or 1 µM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1'-(oxydiethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1-phenyl (2), and 6-phenyl, 4-(1'-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle.

Biological Research, 2015

Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the ... more Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC. Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 μg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 μg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 μg/mL for (1), 34.15 μg/mL for (2) and 45.66 μg/mL for (3), compared to galantamine (IC50 of 8.22 μg/mL) used as positive control. The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.

Natural product communications, 2009

Bioassay-guided fractionation of the stem bark of Symphonia globulifera has yielded three known x... more Bioassay-guided fractionation of the stem bark of Symphonia globulifera has yielded three known xanthones, ugaxanthone (1), mbarraxanthone (2) and gentisein (3), two biflavonoid derivatives named GB2 (4) and manniflavanone GB3 (5), and one new polyoxygenated xanthone with an isoprenoid group, named globulixanthone F (6). The structures of these compounds were elucidated by means of spectroscopic methods. The spectral data of 1 and 2 are reported here for the first time, as well as the antimicrobial activity of globulixanthone F against a range of microorganisms. We also report the total synthesis of the xanthone skeleton.

The Natural Products Journal, 2013

Frontiers in Microbiology, 2015

According to some recent studies, Cameroon is one of the sub-Saharan African countries most affec... more According to some recent studies, Cameroon is one of the sub-Saharan African countries most affected by hepatitis C, with low access to the standard therapy based on the combination of pegylated interferon and ribavirin. A first ethnobotanical survey, conducted in the Western region of Cameroon, reported the use of several medicinal plants in traditional medicine for the healing of liver-related disorders. Crude organic extracts of five plants surveyed were prepared and their effect against hepatitis C virus (HCV) infection investigated. The HCV JFH1 strain cell culture system HCVcc was used. The antiviral activity was quantified by immunofluorescent labeling of HCV E1 envelope protein at 30 h post-infection in the presence of the plant extracts. Active compounds were then tested in time course infection experiments. Dose-response and cellular toxicity assays were also determined. Three extracts, methanol extracts from roots of Trichilia dregeana, stems of Detarium microcarpum and leaves of Phragmanthera capitata, showed anti-HCV activity, with half-maximal inhibitory concentration of 16.16, 1.42, and 13.17 μg/mL, respectively. Huh-7 cells were incubated with the extracts for 72 h and it appears that T. dregeana extract is not toxic up to 200 μg/mL, D. microcarpum up to 100 μg/mL and P. capitata up to 800 μg/mL. All the three extracts showed a strong inhibition of HCV entry and no effect on replication or secretion. Taken together, these results showed that extracts from Cameroonian medicinal plants are promising sources of anti-HCV agents.

The American journal of Chinese medicine, 2014

Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Centra... more Entada africana (Ea) is a medicinal plant from the family of Fabaceae, used in Western and Central Africa regions to treat liver diseases. Antiviral properties of this plant were reported against Hepatitis B virus, while effects against Hepatitis C virus (HCV) remained unknown. This study reports for the first time, the effects of Ea crude extract and fractions on HCV replication. Furthermore, the effect of one Ea fraction on the transcriptional expression of two interferon-stimulated genes (ISGs) was also investigated. A methylene chloride-methanol (MCM) stem bark crude extract and different MCM fractions (EaF0, EaF5, EaF10, EaF25, and EaF100) were prepared and tested on LucUbiNeo-ET and Huh 5.15 cells lines used as genotype 1b (GT1b) replicon systems. The cells were incubated with crude extract and fractions at various concentrations. Then, the antiviral activity was assessed by luciferase reporter assay and the cell viability by MTT assay. Gene expression was also analyzed using ...

Two prenylated xanthone derivatives, named globulixanthones C and D and one bis-xanthone, designa... more Two prenylated xanthone derivatives, named globulixanthones C and D and one bis-xanthone, designated globulixanthone E, have been isolated from the root bark of Symphonia globulifera. The structures of these compounds were elucidated by a detailed spectroscopic analysis. They have been shown to exhibit in vitro significant antimicrobial activity against a range of micro-organisms.

ChemInform, 2014

Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type li... more Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type limonoid TS3 (4), β-sitosterol, and stigmasterol were isolated from the root bark of Trichilia rubescens. Their structures were elucidated by means of extensive spectroscopic analyses, particularly one dimensional (1D)and 2D-NMR techniques in conjunction with mass spectrometry. Rubescins A-C (1-3) and limonoid TS3 (4) were evaluated for their protective effects against oxidative stress induced in HC-04 cells by H 2 O 2 . Compound (1) showed strong inhibitory effects on lactase dehydrogenase (LDH) leakage, being as active (IC 50 value of 0.0026 µM) as the positive control quercetin (IC 50 value of 0.0030 µM).

ChemInform, 2010

Species. -The title compounds (I) and (II) show significant antimicrobial activities against a wi... more Species. -The title compounds (I) and (II) show significant antimicrobial activities against a wide range of bacteria and fungi. -(TSAFFACK, M.; NGUEMEVING, J. R.; KUETE, V.; TCHIZE, B. L. S. N.; MKOUNGA, P.; BENG, V. P.; HULTIN, P. G.; TSAMO, E.; NKENGFACK*, A. E.; Chem.

Natural Product Research, 2011

This study was designed at evaluating the antimycobacterial, antibacterial and antifungal activit... more This study was designed at evaluating the antimycobacterial, antibacterial and antifungal activities of the CH2Cl2-CH3OH (1:1) extracts and isolated compounds, namely 3,4-dimethoxy-3',4'-methylenedioxy-7,7'-epoxylignan (1), genkwainin (2), pycnanthulignene C (3), 4,5-dimethoxy-3',4'-methylenedioxy-2,7'-cycloligna-7,7'-diene (4), pycnanthulignene A (5) from the roots, and calycosin (6), biochanin A (7) and prunetin (8), from the fruits of Pycnanthus angolensis. The microplate alamar blue assay and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration of the samples. The H+-ATPase-mediated proton pumping assay was used to evaluate one of the possible mechanisms of action of the extracts and isolated compounds. The results of MIC determinations showed that the extract from roots was able to prevent the growth of all the studied organisms, including mycobacteria, fungi, and Gram-positive and Gram-negative bacteria. All tested compounds showed antimicrobial activities to different extents, compound 1 and 8 exhibiting the best antimicrobial spectrum, with 92.3% of the tested organisms being sensitive. The results obtained in this study also showed that the extracts as well as most of the compounds were able to inhibit the H(+)-ATPase activity. The overall results provided evidence that P. angolensis and some of its components might be potential sources of antimicrobial drugs against tuberculosis, bacterial and fungal diseases.

Journal of Natural Products, 2002

Bioassay-guided fractionation of a root bark extract of Symphonia globulifera has yielded, in add... more Bioassay-guided fractionation of a root bark extract of Symphonia globulifera has yielded, in addition to stigmasterol, two new xanthones with isoprenoid units, named globulixanthones A (1) and B (2). The structures of these compounds have been elucidated by spectroscopic means. They possess significant cytotoxicity in vitro against the KB cell line.

CHEMICAL & PHARMACEUTICAL BULLETIN, 2010

Three new olean-12-ene derivatives (1-3), together with known urs-12-ene-3beta, 28-diol (4) were ... more Three new olean-12-ene derivatives (1-3), together with known urs-12-ene-3beta, 28-diol (4) were isolated from the stem root of Cylicodiscus gabunensis. The structures of the new compounds were established by chemical and spectroscopic means as beta-amyrin-n-nonyl ether (1), 22alpha-hydroxyolean-12-en-3beta-yl-beta-D-galactopyranoside (2), and 24-hydroxyolean-12-en-3beta-yl-beta-D-glucopyranoside (3).