Phytochemical investigation of the aerial parts of Salvia eremophila led to the isolation of a lu... more Phytochemical investigation of the aerial parts of Salvia eremophila led to the isolation of a lupane triterpenoid, 3β, 20-dihydroxylupane-28-oic acid (1), together with eight other compounds, comprising three diterpene, two triterpene, two flavonoids and a steroidal glucoside. Their structures were elucidated by interpretation of their one-dimensional and two-dimensional NMR spectra and completed by the analysis of the HRESIMS data. Compounds 1, 2-4 and 8 were evaluated for their cytotoxicities against five human tumour cell lines. Compounds 1 and 3 hold a good potential for use in future studies due to their anti-cancer properties.
Fractionation of an acetone extract of the aerial parts of Salvia urmiensis led to the isolation ... more Fractionation of an acetone extract of the aerial parts of Salvia urmiensis led to the isolation of a new (1) and a known (2) E-seco-ursane-type triterpenoid, together with four other known compounds. Their structures were established by 1D and 2D nuclear magnetic resonance as well as high-resolution electrospray ionization mass spectrometry. The effect of compounds 1 and 2 on cell viability of HeLa and HepG2 cells was investigated with the MTT assay. We also report the mechanism of action of compound 2 as a potential anticancer agent in HeLa cells. Bcl-2, Bax, and caspases signaling pathway expression in HeLa cells was analyzed. HeLa cells treated with compound 2 were assayed for the cleavage of poly-(ADP-ribose)-polymerase and DNA fragmentation resulting in nuclear shrinkage. Taken together, these results suggest that treatment of HeLa cells with compound 2 can induce apoptosis by regulating Bcl-2 family members and by suppressing caspase cascade activation.
Phytochemical investigation of the roots of Salvia chloroleuca led to the isolation and identific... more Phytochemical investigation of the roots of Salvia chloroleuca led to the isolation and identification of a new rearranged abietane diterpenoid (1). Its structure was elucidated by interpretation of the 1D and 2D NMR spectra and completed by the analysis of the HR-ESI-MS data. Compound 1 is the secondly reported compound on a rearranged tricyclic abietane (4,5-seco-5,10-friedo-abietane) diterpenoid with a ketal functionality between C-2 and C-11. A plausible biosynthetic pathway of 1 was also proposed.
The antimicrobial activities of 44 methanolic extracts from different parts of Iranian indigenous... more The antimicrobial activities of 44 methanolic extracts from different parts of Iranian indigenous plant species used in traditional medicines of Iran were tested against a panel of 35 pathogenic and multiresistant bacteria and 1 yeast. The antimicrobial efficacy was determined using Müller-Hinton agar in Petri dishes seeded by a multiple inoculator and minimal inhibition concentration (MIC) method. The 21 most active extracts (MIC < 0·3 mg ml(-1) for one or several micro-organisms) were submitted to a more refined measurement. The best antibacterial activity was obtained by 10 plants. Microdilution assays allowed to determinate the MIC and MBC of the 21 most active extracts. The lowest achieved MIC value was 78 μg ml(-1), with 4 extracts. This work confirms the antimicrobial activity of assayed plants and suggests further examination to identify the chemical structure of their antimicrobial compounds. Significance and impact of the study: This study describes the antimicrobial sc...
Three labdane diterpenoids, 14α-hydroxy-15-chlorosclareol (1), 14α-hydroxy-15-acetoxysclareol (2)... more Three labdane diterpenoids, 14α-hydroxy-15-chlorosclareol (1), 14α-hydroxy-15-acetoxysclareol (2), and 6β-hydroxy-14α-epoxysclareol (3), together with the known diterpenoids sclareol (4), 6β-hydroxysclareol (5), and 14α-epoxysclareol (6), as well as other common plant constituents were isolated from the n-hexane extract of aerial parts of Salvia reuterana. The structures of the new compounds were established by extensive 1D and 2D NMR spectroscopic techniques. Compound 1 is the first example of a halogenated terpenoid in the genus Salvia. Compounds 1-6 were also tested for their inhibitory activity toward HeLa and MCF-7 cell lines. Preliminary structure-activity relationship studies indicated that double bond moiety in sclareol is an essential feature for activity and modification of this moiety significantly decreased the cytotoxic activity of the resulting compounds.
Three new sesterterpene lactones, lachnocalyxolide A-C [1, 2, and 3 (as epimeric pair)] together ... more Three new sesterterpene lactones, lachnocalyxolide A-C [1, 2, and 3 (as epimeric pair)] together with nine known compounds, including two sesterterpenoids, three flavonoids, two steroidal compounds, one nor diterpenoid and one triterpenoid, were isolated from the acetone extract of the aerial parts of Salvia lachnocalyx Hedge. Their structures were elucidated on the basis of extensive spectroscopic data, including 1D and 2D NMR spectra, as well as HR-ESI-MS. Compounds 1, 2, 4 and 5 were also tested for their inhibitory activity toward MCF-7 and HeLa cell lines.
Calycopterin is a flavonoid compound isolated from Dracocephalum kotschyi that has multiple medic... more Calycopterin is a flavonoid compound isolated from Dracocephalum kotschyi that has multiple medical uses, as an antispasmodic, analgesic, anti-hyperlipidemic, and immunomodulatory agents. However, its biological activity and the mechanism of action are poorly investigated. Herein, we investigated the apoptotic effect of calycopterin against the human hepatoblastoma cancer cell (HepG2) line. We discovered that calycopterin-treated HepG2 cells were killed off by apoptosis in a dose-dependent manner within 24 h, and was characterized by the appearance of nuclear shrinkage, cleavage of poly (ADP-ribose) polymerase and DNA fragmentation. Calycopterin treatment also affected HepG2 cell viability: (a) by inhibiting cell cycle progression at the G2/M transition leading to growth arrest and apoptosis; (b) by decreasing the expression of mitotic kinase cdc2, mitotic phosphatase cdc25c, mitotic cyclin B1, and apoptotic factors pro-caspases-3 and -9; and (c) increasing the levels of mitochondri...
ABSTRACT Ethnopharmacological relevance Salvia sahendica has been traditionally used for antibact... more ABSTRACT Ethnopharmacological relevance Salvia sahendica has been traditionally used for antibacterial, anti-fungal, and anti-cancer purposes and treatment of dyspepsia in many parts of Iran. Aim of the study Our aim was to investigate the mechanism by which daucosterol a β-sitosterol glycoside isolated from S. sahendica induced apoptosis against human breast adenocarcinoma MCF-7 cells. Methods MCF-7 cells were treated with 5, 10, 20 and 40 μM of daucosterol for 24 h, and proliferation, cytotoxicity, and apoptosis in human breast adenocarcinoma MCF-7 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) leakage assay, acridine orange (AO)/ethidium bromide (EB) double staining and flow cytometry. Phosphoinositide 3-kinase (PI3K), p-Akt, poly (ADP-ribose) polymerase (PARP), Bax, Bcl2, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and cytochrome c were analyzed by western blotting and mRNA expression of PTEN was detected by RT-PCR. Results The results showed that daucosterol suppresses the proliferation and induces the cell cytotoxicity of MCF-7 cells in a dose-dependent manner. Cells treated with different concentrations of daucosterol also showed changes typical of apoptosis: morphological changes and DNA damage. Further analysis revealed a modulation of Bax, Bcl2, and PARP as well as losing mitochondrial membrane potential, and cytochrome c (Cyt c) release in breast cancer cells induced by daucosterol. Our results also showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via upregulation of the PTEN gene and inhibition of the PI3K/Akt pathway. To further explore the proapoptotic mechanism of daucosterol, we investigated the role of the reactive oxygen species (ROS) in the apoptosis induced by daucosterol in MCF-7 cells. The generation of ROS was about 6 to 8-fold as compared to control cells after treatment with daucosterol (20 and 40 μM) for 24 h. Glutathione (GSH) depletion was consistent with ROS generation after treatment with daucosterol. Reversal of apoptosis in antioxidant (NAC and catalase) pretreated cells indicated the involvement of ROS in daucosterol-induced apoptosis. Conclusion Taken together, our results suggest that daucosterol significantly inhibits the growth and induces the apoptosis of human breast cancer cells in vitro.
ABSTRACT The genus Salvia is a rich source of terpenoids with structural diversity. Apart from se... more ABSTRACT The genus Salvia is a rich source of terpenoids with structural diversity. Apart from sesterterpenoids as unusual constituents of Salvia species [1,2], it is a source of di- and triterpenoids with unprecedented carbon skeletons [3]. Aiming at identifying structurally interesting and bioactive metabolites from the Salvia species, we examined the extract of Salvia hydrangea DC. ex Benth. In our search for new bioactive natural products, a novel triterpenoid (hydrangdione C, 1) was isolated from the hexane extract of this plant. The skeletal type displayed by hydrangdione C was noticeable for its unusual carbon ring skeleton with a unique five membered ring D substituted by an acetyl group. This is the first report of a natural triterpenoid with a five-membered ring D. The structure of 1 was established by comprehensive 1D NMR, 2D NMR, and HRMS spectroscopic analysis and subsequently confirmed by a single-crystal X-ray diffraction study. A plausible biosynthetic pathway for 1 was proposed. The formation of 1 could be explained through a pathway including a [3 + 2] cycloaddition type reaction between a monoterpenic unit (trans-β-ocimene) and a diterpenic unit (an icetexone precursor) followed by an oxidation reaction.
Phytochemical investigation of the aerial parts of Salvia eremophila led to the isolation of a lu... more Phytochemical investigation of the aerial parts of Salvia eremophila led to the isolation of a lupane triterpenoid, 3β, 20-dihydroxylupane-28-oic acid (1), together with eight other compounds, comprising three diterpene, two triterpene, two flavonoids and a steroidal glucoside. Their structures were elucidated by interpretation of their one-dimensional and two-dimensional NMR spectra and completed by the analysis of the HRESIMS data. Compounds 1, 2-4 and 8 were evaluated for their cytotoxicities against five human tumour cell lines. Compounds 1 and 3 hold a good potential for use in future studies due to their anti-cancer properties.
Fractionation of an acetone extract of the aerial parts of Salvia urmiensis led to the isolation ... more Fractionation of an acetone extract of the aerial parts of Salvia urmiensis led to the isolation of a new (1) and a known (2) E-seco-ursane-type triterpenoid, together with four other known compounds. Their structures were established by 1D and 2D nuclear magnetic resonance as well as high-resolution electrospray ionization mass spectrometry. The effect of compounds 1 and 2 on cell viability of HeLa and HepG2 cells was investigated with the MTT assay. We also report the mechanism of action of compound 2 as a potential anticancer agent in HeLa cells. Bcl-2, Bax, and caspases signaling pathway expression in HeLa cells was analyzed. HeLa cells treated with compound 2 were assayed for the cleavage of poly-(ADP-ribose)-polymerase and DNA fragmentation resulting in nuclear shrinkage. Taken together, these results suggest that treatment of HeLa cells with compound 2 can induce apoptosis by regulating Bcl-2 family members and by suppressing caspase cascade activation.
Phytochemical investigation of the roots of Salvia chloroleuca led to the isolation and identific... more Phytochemical investigation of the roots of Salvia chloroleuca led to the isolation and identification of a new rearranged abietane diterpenoid (1). Its structure was elucidated by interpretation of the 1D and 2D NMR spectra and completed by the analysis of the HR-ESI-MS data. Compound 1 is the secondly reported compound on a rearranged tricyclic abietane (4,5-seco-5,10-friedo-abietane) diterpenoid with a ketal functionality between C-2 and C-11. A plausible biosynthetic pathway of 1 was also proposed.
The antimicrobial activities of 44 methanolic extracts from different parts of Iranian indigenous... more The antimicrobial activities of 44 methanolic extracts from different parts of Iranian indigenous plant species used in traditional medicines of Iran were tested against a panel of 35 pathogenic and multiresistant bacteria and 1 yeast. The antimicrobial efficacy was determined using Müller-Hinton agar in Petri dishes seeded by a multiple inoculator and minimal inhibition concentration (MIC) method. The 21 most active extracts (MIC < 0·3 mg ml(-1) for one or several micro-organisms) were submitted to a more refined measurement. The best antibacterial activity was obtained by 10 plants. Microdilution assays allowed to determinate the MIC and MBC of the 21 most active extracts. The lowest achieved MIC value was 78 μg ml(-1), with 4 extracts. This work confirms the antimicrobial activity of assayed plants and suggests further examination to identify the chemical structure of their antimicrobial compounds. Significance and impact of the study: This study describes the antimicrobial sc...
Three labdane diterpenoids, 14α-hydroxy-15-chlorosclareol (1), 14α-hydroxy-15-acetoxysclareol (2)... more Three labdane diterpenoids, 14α-hydroxy-15-chlorosclareol (1), 14α-hydroxy-15-acetoxysclareol (2), and 6β-hydroxy-14α-epoxysclareol (3), together with the known diterpenoids sclareol (4), 6β-hydroxysclareol (5), and 14α-epoxysclareol (6), as well as other common plant constituents were isolated from the n-hexane extract of aerial parts of Salvia reuterana. The structures of the new compounds were established by extensive 1D and 2D NMR spectroscopic techniques. Compound 1 is the first example of a halogenated terpenoid in the genus Salvia. Compounds 1-6 were also tested for their inhibitory activity toward HeLa and MCF-7 cell lines. Preliminary structure-activity relationship studies indicated that double bond moiety in sclareol is an essential feature for activity and modification of this moiety significantly decreased the cytotoxic activity of the resulting compounds.
Three new sesterterpene lactones, lachnocalyxolide A-C [1, 2, and 3 (as epimeric pair)] together ... more Three new sesterterpene lactones, lachnocalyxolide A-C [1, 2, and 3 (as epimeric pair)] together with nine known compounds, including two sesterterpenoids, three flavonoids, two steroidal compounds, one nor diterpenoid and one triterpenoid, were isolated from the acetone extract of the aerial parts of Salvia lachnocalyx Hedge. Their structures were elucidated on the basis of extensive spectroscopic data, including 1D and 2D NMR spectra, as well as HR-ESI-MS. Compounds 1, 2, 4 and 5 were also tested for their inhibitory activity toward MCF-7 and HeLa cell lines.
Calycopterin is a flavonoid compound isolated from Dracocephalum kotschyi that has multiple medic... more Calycopterin is a flavonoid compound isolated from Dracocephalum kotschyi that has multiple medical uses, as an antispasmodic, analgesic, anti-hyperlipidemic, and immunomodulatory agents. However, its biological activity and the mechanism of action are poorly investigated. Herein, we investigated the apoptotic effect of calycopterin against the human hepatoblastoma cancer cell (HepG2) line. We discovered that calycopterin-treated HepG2 cells were killed off by apoptosis in a dose-dependent manner within 24 h, and was characterized by the appearance of nuclear shrinkage, cleavage of poly (ADP-ribose) polymerase and DNA fragmentation. Calycopterin treatment also affected HepG2 cell viability: (a) by inhibiting cell cycle progression at the G2/M transition leading to growth arrest and apoptosis; (b) by decreasing the expression of mitotic kinase cdc2, mitotic phosphatase cdc25c, mitotic cyclin B1, and apoptotic factors pro-caspases-3 and -9; and (c) increasing the levels of mitochondri...
ABSTRACT Ethnopharmacological relevance Salvia sahendica has been traditionally used for antibact... more ABSTRACT Ethnopharmacological relevance Salvia sahendica has been traditionally used for antibacterial, anti-fungal, and anti-cancer purposes and treatment of dyspepsia in many parts of Iran. Aim of the study Our aim was to investigate the mechanism by which daucosterol a β-sitosterol glycoside isolated from S. sahendica induced apoptosis against human breast adenocarcinoma MCF-7 cells. Methods MCF-7 cells were treated with 5, 10, 20 and 40 μM of daucosterol for 24 h, and proliferation, cytotoxicity, and apoptosis in human breast adenocarcinoma MCF-7 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) leakage assay, acridine orange (AO)/ethidium bromide (EB) double staining and flow cytometry. Phosphoinositide 3-kinase (PI3K), p-Akt, poly (ADP-ribose) polymerase (PARP), Bax, Bcl2, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and cytochrome c were analyzed by western blotting and mRNA expression of PTEN was detected by RT-PCR. Results The results showed that daucosterol suppresses the proliferation and induces the cell cytotoxicity of MCF-7 cells in a dose-dependent manner. Cells treated with different concentrations of daucosterol also showed changes typical of apoptosis: morphological changes and DNA damage. Further analysis revealed a modulation of Bax, Bcl2, and PARP as well as losing mitochondrial membrane potential, and cytochrome c (Cyt c) release in breast cancer cells induced by daucosterol. Our results also showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via upregulation of the PTEN gene and inhibition of the PI3K/Akt pathway. To further explore the proapoptotic mechanism of daucosterol, we investigated the role of the reactive oxygen species (ROS) in the apoptosis induced by daucosterol in MCF-7 cells. The generation of ROS was about 6 to 8-fold as compared to control cells after treatment with daucosterol (20 and 40 μM) for 24 h. Glutathione (GSH) depletion was consistent with ROS generation after treatment with daucosterol. Reversal of apoptosis in antioxidant (NAC and catalase) pretreated cells indicated the involvement of ROS in daucosterol-induced apoptosis. Conclusion Taken together, our results suggest that daucosterol significantly inhibits the growth and induces the apoptosis of human breast cancer cells in vitro.
ABSTRACT The genus Salvia is a rich source of terpenoids with structural diversity. Apart from se... more ABSTRACT The genus Salvia is a rich source of terpenoids with structural diversity. Apart from sesterterpenoids as unusual constituents of Salvia species [1,2], it is a source of di- and triterpenoids with unprecedented carbon skeletons [3]. Aiming at identifying structurally interesting and bioactive metabolites from the Salvia species, we examined the extract of Salvia hydrangea DC. ex Benth. In our search for new bioactive natural products, a novel triterpenoid (hydrangdione C, 1) was isolated from the hexane extract of this plant. The skeletal type displayed by hydrangdione C was noticeable for its unusual carbon ring skeleton with a unique five membered ring D substituted by an acetyl group. This is the first report of a natural triterpenoid with a five-membered ring D. The structure of 1 was established by comprehensive 1D NMR, 2D NMR, and HRMS spectroscopic analysis and subsequently confirmed by a single-crystal X-ray diffraction study. A plausible biosynthetic pathway for 1 was proposed. The formation of 1 could be explained through a pathway including a [3 + 2] cycloaddition type reaction between a monoterpenic unit (trans-β-ocimene) and a diterpenic unit (an icetexone precursor) followed by an oxidation reaction.
Uploads
Papers by Moridi Farimani