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Ikhlas A. Khan - One of the best experts on this subject based on the ideXlab platform.
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Metabolic Profiling of Hoodia, Chamomile, Terminalia Species and Evaluation of Commercial Preparations Using Ultrahigh-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry
Planta Medica, 2017Co-Authors: Bharathi Avula, Mark Wrona, G. Isaac, Jimmy Yuk, Kate Yu, Yan-hong Wang, Ikhlas A. KhanAbstract:Ultrahigh-performance liquid chromatography quadrupole- time-of-flight mass spectrometry (UHPLC-QToF‑MS) profiling was used for the identification of marker compounds and generation of metabolic patterns that could be interrogated using chemometric modeling software. UHPLC-QToF‑MS was used to generate comprehensive fingerprints of three botani- cals (Hoodia, Terminalia, and chamomile), each having differ- ent classes of compounds. Detection of a broad range of ions was carried out in full scan mode in both positive and negative modes over the range m/z 100–1700 using high-resolution mass spectrometry. Multivariate statistical analysis was used to extract relevant chemical information from the data to easily differentiate between Terminalia species, chamomile varieties, and quality control of Hoodia products. Using non- targeted analysis, identification of 37 compounds contributed to the differences between Terminalia species, 26 flavonoids were identified to show the differences between German and Roman chamomile, and 43 pregnane glycosides were identified from Hoodia gordonii samples. The UHPLC- QToF‑MS-based chemical fingerprinting with principal com- ponent analysis was able to correctly distinguish botanicals and their commercial products. This work can be used as a basis to assure the quality of botanicals and commercial prod- ucts.
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Development of A Generic UPLC/MS Workflow for the Authentication ofHoodia Gardonii Based on Comprehensive Chemical Fingerprinting
The Open Conference Proceedings Journal, 2013Co-Authors: Bharathi Avula, Kate Yu, Yan-hong Wang, Dominic Moore, Warren Potts, Ikhlas A. KhanAbstract:Introduction: In recent years, Hoodia plant and the preparations of Hoodia have become increasingly popular. These dietary supplements are promoted for weight loss. The limited availability of this plant material and its increasing popularity leads to the possibility of adulterations by other species or even genera. Previous results of screenings give rise to serious concerns about the safety of commercial products claimed to be Hoodia, as a considerable amount seems to lack Hoodia. There is a strong need to develop an effective analytical protocol that can be routinely used to authenticate either plant extracts or commercial products that claimed to contain Hoodia gordonii.
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14β hydroxypregnanes from succulent plants belonging to Hoodia gordonii and caralluma genus extraction biological activities and synthesis
Studies in natural products chemistry, 2013Co-Authors: Yatin J Shukla, Ikhlas A. Khan, P Geoffroy, Michel MieschAbstract:Abstract Caralluma and Hoodia are genera of succulent plants belonging to the subfamily of Asclepiadoideae in the family of Apocynaceae. Caralluma is distributed in dry regions of tropical Asia and Africa, majority of species being indigenous to the Indian subcontinent and the Arabian Peninsula. The genus Hoodia is mainly found in the Kalahari desert regions in Southern Africa. We focus on Caralluma adscendens var. fimbriata and Hoodia gordonii due to their popularity and growing commercial interest during the past 20 years. Indeed, it was claimed that these succulent plants contain bioactive compounds, especially 14β-hydroxypregnane derivatives, which showed appetite-suppressant activity and weight loss properties. This chapter describes the isolation, biological properties, and synthesis of 14β-hydroxypregnane derivatives found in C. adscendens var. fimbriata and H. gordonii .
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NMR fingerprinting for analysis of Hoodia species and Hoodia dietary products.
Planta medica, 2010Co-Authors: Jianping Zhao, Bharathi Avula, Yan-hong Wang, Vaishali C Joshi, Natascha Techen, Troy J Smillie, Ikhlas A. KhanAbstract:Hoodia gordonii, a succulent plant growing in African arid regions, is used as a botanical dietary supplement for weight loss. The increasing concerns on the quality and safety of Hoodia products call for the needs of more science-based information, as well as objective and efficient tools for inspection. In the present study, NMR fingerprinting and multivariate analysis techniques were applied for the identification, discrimination, and quality analysis of Hoodia plant materials and commercial products. Four Hoodia species, namely H. gordonii (five authenticated samples), H. currorii (one authenticated sample), H. parviflora (three authenticated samples), and H. rushii (one authenticated sample), were investigated; the chemicals and characteristic spectral signals that made most contributions for their differentiations were revealed. With the aid of NMR fingerprint analysis, ten Hoodia products sold on the dietary supplement market were assessed for their chemical composition and quality. The study demonstrated that the NMR fingerprinting approach could be a promising and efficient tool for the authentication of botanicals.
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bioavailability pharmacokinetics and tissue distribution of the oxypregnane steroidal glycoside p57as3 p57 from Hoodia gordonii in mouse model
Planta Medica, 2010Co-Authors: Vamsi L M Madgula, Bharathi Avula, Yan-hong Wang, Ikhlas A. Khan, Mohammad K Ashfaq, Larry A Walker, Shabana I KhanAbstract:: P57AS3 (P57), an oxypregnane steroidal glycoside, is known to be responsible for the appetite suppressing activity of Hoodia gordonii, a dietary supplement used for weight loss. In this study, bioavailability, pharmacokinetics, and tissue distribution of P57 were determined in CD1 female mice after administration of a single dose of enriched methanolic extract of Hoodia gordonii (equivalent to a dose of 25 mg of P57/kg) by oral gavage or a single dose of purified P57 (25 mg/kg) intravenously. The level of P57 in plasma and tissues (brain, liver, kidney, and intestine) was determined by UPLC-MS. After oral administration of Hoodia extract, the peak plasma level of P57 was achieved in 0.6 h. Upon intravenous administration, the plasma clearance rate of P57 was 1.09 L/h/kg. P57 was rapidly distributed and eliminated from the tissues within 4 hours. The level of tissue distribution was highest in the kidney followed by liver and brain. Upon oral administration, P57 was not detected in the brain and a very low concentration was seen in the intestine, kidney, and liver. Tissue/plasma ratio was 0.33 for brain, 0.57 for liver, and 0.75 for kidney with IV route and 0.11 for intestine, 0.02 for liver, and 0.04 for kidney with oral route. The half-life of the elimination phase was similar with both routes. The oral bioavailability was 47.5 % and the half-life of the absorption phase was 0.13 h. In conclusion, P57 showed moderate bioavailability and was eliminated rapidly.
Bharathi Avula - One of the best experts on this subject based on the ideXlab platform.
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Metabolic Profiling of Hoodia, Chamomile, Terminalia Species and Evaluation of Commercial Preparations Using Ultrahigh-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry
Planta Medica, 2017Co-Authors: Bharathi Avula, Mark Wrona, G. Isaac, Jimmy Yuk, Kate Yu, Yan-hong Wang, Ikhlas A. KhanAbstract:Ultrahigh-performance liquid chromatography quadrupole- time-of-flight mass spectrometry (UHPLC-QToF‑MS) profiling was used for the identification of marker compounds and generation of metabolic patterns that could be interrogated using chemometric modeling software. UHPLC-QToF‑MS was used to generate comprehensive fingerprints of three botani- cals (Hoodia, Terminalia, and chamomile), each having differ- ent classes of compounds. Detection of a broad range of ions was carried out in full scan mode in both positive and negative modes over the range m/z 100–1700 using high-resolution mass spectrometry. Multivariate statistical analysis was used to extract relevant chemical information from the data to easily differentiate between Terminalia species, chamomile varieties, and quality control of Hoodia products. Using non- targeted analysis, identification of 37 compounds contributed to the differences between Terminalia species, 26 flavonoids were identified to show the differences between German and Roman chamomile, and 43 pregnane glycosides were identified from Hoodia gordonii samples. The UHPLC- QToF‑MS-based chemical fingerprinting with principal com- ponent analysis was able to correctly distinguish botanicals and their commercial products. This work can be used as a basis to assure the quality of botanicals and commercial prod- ucts.
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Development of A Generic UPLC/MS Workflow for the Authentication ofHoodia Gardonii Based on Comprehensive Chemical Fingerprinting
The Open Conference Proceedings Journal, 2013Co-Authors: Bharathi Avula, Kate Yu, Yan-hong Wang, Dominic Moore, Warren Potts, Ikhlas A. KhanAbstract:Introduction: In recent years, Hoodia plant and the preparations of Hoodia have become increasingly popular. These dietary supplements are promoted for weight loss. The limited availability of this plant material and its increasing popularity leads to the possibility of adulterations by other species or even genera. Previous results of screenings give rise to serious concerns about the safety of commercial products claimed to be Hoodia, as a considerable amount seems to lack Hoodia. There is a strong need to develop an effective analytical protocol that can be routinely used to authenticate either plant extracts or commercial products that claimed to contain Hoodia gordonii.
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NMR fingerprinting for analysis of Hoodia species and Hoodia dietary products.
Planta medica, 2010Co-Authors: Jianping Zhao, Bharathi Avula, Yan-hong Wang, Vaishali C Joshi, Natascha Techen, Troy J Smillie, Ikhlas A. KhanAbstract:Hoodia gordonii, a succulent plant growing in African arid regions, is used as a botanical dietary supplement for weight loss. The increasing concerns on the quality and safety of Hoodia products call for the needs of more science-based information, as well as objective and efficient tools for inspection. In the present study, NMR fingerprinting and multivariate analysis techniques were applied for the identification, discrimination, and quality analysis of Hoodia plant materials and commercial products. Four Hoodia species, namely H. gordonii (five authenticated samples), H. currorii (one authenticated sample), H. parviflora (three authenticated samples), and H. rushii (one authenticated sample), were investigated; the chemicals and characteristic spectral signals that made most contributions for their differentiations were revealed. With the aid of NMR fingerprint analysis, ten Hoodia products sold on the dietary supplement market were assessed for their chemical composition and quality. The study demonstrated that the NMR fingerprinting approach could be a promising and efficient tool for the authentication of botanicals.
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bioavailability pharmacokinetics and tissue distribution of the oxypregnane steroidal glycoside p57as3 p57 from Hoodia gordonii in mouse model
Planta Medica, 2010Co-Authors: Vamsi L M Madgula, Bharathi Avula, Yan-hong Wang, Ikhlas A. Khan, Mohammad K Ashfaq, Larry A Walker, Shabana I KhanAbstract:: P57AS3 (P57), an oxypregnane steroidal glycoside, is known to be responsible for the appetite suppressing activity of Hoodia gordonii, a dietary supplement used for weight loss. In this study, bioavailability, pharmacokinetics, and tissue distribution of P57 were determined in CD1 female mice after administration of a single dose of enriched methanolic extract of Hoodia gordonii (equivalent to a dose of 25 mg of P57/kg) by oral gavage or a single dose of purified P57 (25 mg/kg) intravenously. The level of P57 in plasma and tissues (brain, liver, kidney, and intestine) was determined by UPLC-MS. After oral administration of Hoodia extract, the peak plasma level of P57 was achieved in 0.6 h. Upon intravenous administration, the plasma clearance rate of P57 was 1.09 L/h/kg. P57 was rapidly distributed and eliminated from the tissues within 4 hours. The level of tissue distribution was highest in the kidney followed by liver and brain. Upon oral administration, P57 was not detected in the brain and a very low concentration was seen in the intestine, kidney, and liver. Tissue/plasma ratio was 0.33 for brain, 0.57 for liver, and 0.75 for kidney with IV route and 0.11 for intestine, 0.02 for liver, and 0.04 for kidney with oral route. The half-life of the elimination phase was similar with both routes. The oral bioavailability was 47.5 % and the half-life of the absorption phase was 0.13 h. In conclusion, P57 showed moderate bioavailability and was eliminated rapidly.
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characterization of in vitro pharmacokinetic properties of hoodigogenin a from Hoodia gordonii
Planta Medica, 2010Co-Authors: Vamsi L M Madgula, Bharathi Avula, Ikhlas A. Khan, Yatin J Shukla, Rahul S Pawar, Larry A Walker, Shabana I KhanAbstract:: This study was aimed to predict the pharmacokinetic properties of hoodigogenin A, which is the aglycone of the oxypregnane steroidal glycoside P57AS3 (P57) isolated from Hoodia gordonii. A series of in vitro assays was used to predict its gastric, intestinal and metabolic stability, intestinal and blood brain barrier (BBB) transport, protein binding and interaction with major drug metabolising enzymes. In the simulated gastric fluid, hoodigogenin A was stable (2 % degradation in 60 minutes) whereas P57 was unstable (45 % degradation in 30 minutes). In simulated intestinal fluid, P57 was degraded to an extent of 8 % in 180 minutes, while hoodigogenin A was stable. Hoodigogenin A was efficiently transported by passive diffusion across Caco-2 and MDR1-MDCK monolayers with P(app) values in the range of 32 x 10(-6) cm/sec and 22 x 10(-6) cm/sec, respectively. The compound was metabolically unstable in human liver microsomes and S9 fractions with a CL' (int) of 71 and 120 mL/min/kg, respectively and was bound to the plasma proteins to an extent of 92 %. The compound strongly inhibited CYP3A4 activity (IC(50) 3 microM), indicating a possibility of drug-herb/botanical interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs/drugs.
Yatin J Shukla - One of the best experts on this subject based on the ideXlab platform.
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14β hydroxypregnanes from succulent plants belonging to Hoodia gordonii and caralluma genus extraction biological activities and synthesis
Studies in natural products chemistry, 2013Co-Authors: Yatin J Shukla, Ikhlas A. Khan, P Geoffroy, Michel MieschAbstract:Abstract Caralluma and Hoodia are genera of succulent plants belonging to the subfamily of Asclepiadoideae in the family of Apocynaceae. Caralluma is distributed in dry regions of tropical Asia and Africa, majority of species being indigenous to the Indian subcontinent and the Arabian Peninsula. The genus Hoodia is mainly found in the Kalahari desert regions in Southern Africa. We focus on Caralluma adscendens var. fimbriata and Hoodia gordonii due to their popularity and growing commercial interest during the past 20 years. Indeed, it was claimed that these succulent plants contain bioactive compounds, especially 14β-hydroxypregnane derivatives, which showed appetite-suppressant activity and weight loss properties. This chapter describes the isolation, biological properties, and synthesis of 14β-hydroxypregnane derivatives found in C. adscendens var. fimbriata and H. gordonii .
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characterization of in vitro pharmacokinetic properties of hoodigogenin a from Hoodia gordonii
Planta Medica, 2010Co-Authors: Vamsi L M Madgula, Bharathi Avula, Ikhlas A. Khan, Yatin J Shukla, Rahul S Pawar, Larry A Walker, Shabana I KhanAbstract:: This study was aimed to predict the pharmacokinetic properties of hoodigogenin A, which is the aglycone of the oxypregnane steroidal glycoside P57AS3 (P57) isolated from Hoodia gordonii. A series of in vitro assays was used to predict its gastric, intestinal and metabolic stability, intestinal and blood brain barrier (BBB) transport, protein binding and interaction with major drug metabolising enzymes. In the simulated gastric fluid, hoodigogenin A was stable (2 % degradation in 60 minutes) whereas P57 was unstable (45 % degradation in 30 minutes). In simulated intestinal fluid, P57 was degraded to an extent of 8 % in 180 minutes, while hoodigogenin A was stable. Hoodigogenin A was efficiently transported by passive diffusion across Caco-2 and MDR1-MDCK monolayers with P(app) values in the range of 32 x 10(-6) cm/sec and 22 x 10(-6) cm/sec, respectively. The compound was metabolically unstable in human liver microsomes and S9 fractions with a CL' (int) of 71 and 120 mL/min/kg, respectively and was bound to the plasma proteins to an extent of 92 %. The compound strongly inhibited CYP3A4 activity (IC(50) 3 microM), indicating a possibility of drug-herb/botanical interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs/drugs.
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pregnane glycosides from Hoodia gordonii
Phytochemistry, 2009Co-Authors: Yatin J Shukla, Rahul S Pawar, Yuanqing Ding, Xingcong Li, Daneel Ferreira, Ikhlas A. KhanAbstract:Abstract Hoodia gordonii is a ‘weight loss’ herb, which has gained popularity in the western countries as an appetite suppressant dietary supplement. Phytochemical study of its aerial parts led to isolation of seven pregnane glycosides (hoodigosides W–Z, hoodistanalosides A–B). Their structures were elucidated by chemical degradation studies and spectroscopic methods, including 1D and 2D NMR and CD spectroscopic methods.
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Chemical fingerprint of Hoodia species, dietary supplements, and related genera by using HPTLC.
IEEE Journal of Solid-state Circuits, 2008Co-Authors: Chidananda Swamy Rumalla, Bharathi Avula, Yan-hong Wang, Yatin J Shukla, Rahul S Pawar, Troy J Smillie, Ikhlas A. KhanAbstract:A HPTLC method was developed for simple and rapid chemical fingerprint analysis of four Hoodia species, dietary supplements that claim to contain Hoodia gordonii, and plants from genera related to Hoodia. HPTLC was performed on precoated silica 60F(254 )plates with dichloromethane/methanol/water 75:17:2.2 by volume, as mobile phase. Evaluation of the HPTLC plates was done by using the CAMAG DigiStore2 digital system with winCATS software. The authentication of H. gordonii was achieved by comparing the band colors and R(f) values for TLC fingerprints with those of 11 standard compounds including P57. The developed method was successfully applied for the identification of the 11 pregnane glycosides for four different species of Hoodia, 24 related genera and 13 dietary supplements that claim to contain H. gordonii. Different sample matrices were successfully analyzed, providing a wide range of applicability for this method, including gels, capsules, tablets, sprays, teas, snack bars, powders, and juices. The developed method was validated for specificity, stability, repeatability, and robustness. The results of HPTLC method were verified by LC-UV-MS method.
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identification and structural characterization of steroidal glycosides in Hoodia gordonii by ion trap tandem mass spectrometry and liquid chromatography coupled with electrospray ionization time of flight mass spectrometry
Rapid Communications in Mass Spectrometry, 2008Co-Authors: Bharathi Avula, Yan-hong Wang, Yatin J Shukla, Rahul S Pawar, T J Smillie, Ikhlas A. KhanAbstract:Electrospray ion-trap tandem mass spectrometry (ESI-MS/MS) and high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (LC/ESI-TOFMS) were used to identify and characterize eight C-21 steroidal glycosides in Hoodia gordonii. A generalized fragmentation pathway was proposed by comparing the spectra acquired for eight C-21 steroidal glycosides. The steroidal glycosides in Hoodia gordonii have been classified into two major core groups: hoodigenin A and calogenin. Using the ESI-TOF method, the major core peak ions generated by hoodigenin A glycosides are m/z 313 and 295 and by calogenin glycosides are m/z 479, 461, 299 and 281, respectively. In the MS/MS spectra, fragmentation reactions of the [M+Na]+ ion were recorded to provide structural information about the glycosyl and aglycone moieties. The data illustrates the ability of positive mode ESI for the identification of hoodigenin A and calogenin glycosides, including the nature of the hoodigenin A and calogenin core, the number of sugar residues and the type of saccharide moiety. Copyright © 2008 John Wiley & Sons, Ltd.
Rahul S Pawar - One of the best experts on this subject based on the ideXlab platform.
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characterization of in vitro pharmacokinetic properties of hoodigogenin a from Hoodia gordonii
Planta Medica, 2010Co-Authors: Vamsi L M Madgula, Bharathi Avula, Ikhlas A. Khan, Yatin J Shukla, Rahul S Pawar, Larry A Walker, Shabana I KhanAbstract:: This study was aimed to predict the pharmacokinetic properties of hoodigogenin A, which is the aglycone of the oxypregnane steroidal glycoside P57AS3 (P57) isolated from Hoodia gordonii. A series of in vitro assays was used to predict its gastric, intestinal and metabolic stability, intestinal and blood brain barrier (BBB) transport, protein binding and interaction with major drug metabolising enzymes. In the simulated gastric fluid, hoodigogenin A was stable (2 % degradation in 60 minutes) whereas P57 was unstable (45 % degradation in 30 minutes). In simulated intestinal fluid, P57 was degraded to an extent of 8 % in 180 minutes, while hoodigogenin A was stable. Hoodigogenin A was efficiently transported by passive diffusion across Caco-2 and MDR1-MDCK monolayers with P(app) values in the range of 32 x 10(-6) cm/sec and 22 x 10(-6) cm/sec, respectively. The compound was metabolically unstable in human liver microsomes and S9 fractions with a CL' (int) of 71 and 120 mL/min/kg, respectively and was bound to the plasma proteins to an extent of 92 %. The compound strongly inhibited CYP3A4 activity (IC(50) 3 microM), indicating a possibility of drug-herb/botanical interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs/drugs.
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pregnane glycosides from Hoodia gordonii
Phytochemistry, 2009Co-Authors: Yatin J Shukla, Rahul S Pawar, Yuanqing Ding, Xingcong Li, Daneel Ferreira, Ikhlas A. KhanAbstract:Abstract Hoodia gordonii is a ‘weight loss’ herb, which has gained popularity in the western countries as an appetite suppressant dietary supplement. Phytochemical study of its aerial parts led to isolation of seven pregnane glycosides (hoodigosides W–Z, hoodistanalosides A–B). Their structures were elucidated by chemical degradation studies and spectroscopic methods, including 1D and 2D NMR and CD spectroscopic methods.
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Chemical fingerprint of Hoodia species, dietary supplements, and related genera by using HPTLC.
IEEE Journal of Solid-state Circuits, 2008Co-Authors: Chidananda Swamy Rumalla, Bharathi Avula, Yan-hong Wang, Yatin J Shukla, Rahul S Pawar, Troy J Smillie, Ikhlas A. KhanAbstract:A HPTLC method was developed for simple and rapid chemical fingerprint analysis of four Hoodia species, dietary supplements that claim to contain Hoodia gordonii, and plants from genera related to Hoodia. HPTLC was performed on precoated silica 60F(254 )plates with dichloromethane/methanol/water 75:17:2.2 by volume, as mobile phase. Evaluation of the HPTLC plates was done by using the CAMAG DigiStore2 digital system with winCATS software. The authentication of H. gordonii was achieved by comparing the band colors and R(f) values for TLC fingerprints with those of 11 standard compounds including P57. The developed method was successfully applied for the identification of the 11 pregnane glycosides for four different species of Hoodia, 24 related genera and 13 dietary supplements that claim to contain H. gordonii. Different sample matrices were successfully analyzed, providing a wide range of applicability for this method, including gels, capsules, tablets, sprays, teas, snack bars, powders, and juices. The developed method was validated for specificity, stability, repeatability, and robustness. The results of HPTLC method were verified by LC-UV-MS method.
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identification and structural characterization of steroidal glycosides in Hoodia gordonii by ion trap tandem mass spectrometry and liquid chromatography coupled with electrospray ionization time of flight mass spectrometry
Rapid Communications in Mass Spectrometry, 2008Co-Authors: Bharathi Avula, Yan-hong Wang, Yatin J Shukla, Rahul S Pawar, T J Smillie, Ikhlas A. KhanAbstract:Electrospray ion-trap tandem mass spectrometry (ESI-MS/MS) and high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (LC/ESI-TOFMS) were used to identify and characterize eight C-21 steroidal glycosides in Hoodia gordonii. A generalized fragmentation pathway was proposed by comparing the spectra acquired for eight C-21 steroidal glycosides. The steroidal glycosides in Hoodia gordonii have been classified into two major core groups: hoodigenin A and calogenin. Using the ESI-TOF method, the major core peak ions generated by hoodigenin A glycosides are m/z 313 and 295 and by calogenin glycosides are m/z 479, 461, 299 and 281, respectively. In the MS/MS spectra, fragmentation reactions of the [M+Na]+ ion were recorded to provide structural information about the glycosyl and aglycone moieties. The data illustrates the ability of positive mode ESI for the identification of hoodigenin A and calogenin glycosides, including the nature of the hoodigenin A and calogenin core, the number of sugar residues and the type of saccharide moiety. Copyright © 2008 John Wiley & Sons, Ltd.
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hoodigogenin a from Hoodia gordonii
Acta Crystallographica Section E-structure Reports Online, 2008Co-Authors: Yatin J Shukla, Rahul S Pawar, Frank R Fronczek, Ikhlas A. KhanAbstract:The title molecule (systematic name: 12-O-β-tigloyl-3β,14β-dihydroxypregn-5-en-20-one), C26H38O5, isolated from aerial parts of Hoodia gordonii, has its steroid A and C rings in chair conformations, its B ring in a half-chair conformation, and its five-membered ring in an envelope conformation. The OH group at the C/D ring junction forms an intramolecular hydrogen bond with the keto substituent. The OH group on the A ring forms an intermolecular hydrogen bond with the tiglate C=O group, propagating [010] chains in the crystal structure.
Shabana I Khan - One of the best experts on this subject based on the ideXlab platform.
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bioavailability pharmacokinetics and tissue distribution of the oxypregnane steroidal glycoside p57as3 p57 from Hoodia gordonii in mouse model
Planta Medica, 2010Co-Authors: Vamsi L M Madgula, Bharathi Avula, Yan-hong Wang, Ikhlas A. Khan, Mohammad K Ashfaq, Larry A Walker, Shabana I KhanAbstract:: P57AS3 (P57), an oxypregnane steroidal glycoside, is known to be responsible for the appetite suppressing activity of Hoodia gordonii, a dietary supplement used for weight loss. In this study, bioavailability, pharmacokinetics, and tissue distribution of P57 were determined in CD1 female mice after administration of a single dose of enriched methanolic extract of Hoodia gordonii (equivalent to a dose of 25 mg of P57/kg) by oral gavage or a single dose of purified P57 (25 mg/kg) intravenously. The level of P57 in plasma and tissues (brain, liver, kidney, and intestine) was determined by UPLC-MS. After oral administration of Hoodia extract, the peak plasma level of P57 was achieved in 0.6 h. Upon intravenous administration, the plasma clearance rate of P57 was 1.09 L/h/kg. P57 was rapidly distributed and eliminated from the tissues within 4 hours. The level of tissue distribution was highest in the kidney followed by liver and brain. Upon oral administration, P57 was not detected in the brain and a very low concentration was seen in the intestine, kidney, and liver. Tissue/plasma ratio was 0.33 for brain, 0.57 for liver, and 0.75 for kidney with IV route and 0.11 for intestine, 0.02 for liver, and 0.04 for kidney with oral route. The half-life of the elimination phase was similar with both routes. The oral bioavailability was 47.5 % and the half-life of the absorption phase was 0.13 h. In conclusion, P57 showed moderate bioavailability and was eliminated rapidly.
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characterization of in vitro pharmacokinetic properties of hoodigogenin a from Hoodia gordonii
Planta Medica, 2010Co-Authors: Vamsi L M Madgula, Bharathi Avula, Ikhlas A. Khan, Yatin J Shukla, Rahul S Pawar, Larry A Walker, Shabana I KhanAbstract:: This study was aimed to predict the pharmacokinetic properties of hoodigogenin A, which is the aglycone of the oxypregnane steroidal glycoside P57AS3 (P57) isolated from Hoodia gordonii. A series of in vitro assays was used to predict its gastric, intestinal and metabolic stability, intestinal and blood brain barrier (BBB) transport, protein binding and interaction with major drug metabolising enzymes. In the simulated gastric fluid, hoodigogenin A was stable (2 % degradation in 60 minutes) whereas P57 was unstable (45 % degradation in 30 minutes). In simulated intestinal fluid, P57 was degraded to an extent of 8 % in 180 minutes, while hoodigogenin A was stable. Hoodigogenin A was efficiently transported by passive diffusion across Caco-2 and MDR1-MDCK monolayers with P(app) values in the range of 32 x 10(-6) cm/sec and 22 x 10(-6) cm/sec, respectively. The compound was metabolically unstable in human liver microsomes and S9 fractions with a CL' (int) of 71 and 120 mL/min/kg, respectively and was bound to the plasma proteins to an extent of 92 %. The compound strongly inhibited CYP3A4 activity (IC(50) 3 microM), indicating a possibility of drug-herb/botanical interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs/drugs.
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in vitro metabolic stability and intestinal transport of p57as3 p57 from Hoodia gordonii and its interaction with drug metabolizing enzymes
Planta Medica, 2008Co-Authors: Vamsi L M Madgula, Bharathi Avula, Ikhlas A. Khan, Yatin J Shukla, Rahul S Pawar, Larry A Walker, Shabana I KhanAbstract:Hoodia gordonii, a succulent cactus-like plant growing in South Africa, has been used in traditional medicine for its appetite suppressant properties. Its use as a dietary supplement to promote weight loss has recently gained popularity. An oxypregnane steroidal glycoside P57AS3 (P57) is reported to be the active constituent of the sap extract responsible for anorexigenic activity. No information is available about its metabolic stability, intestinal transport and interaction with drug metabolizing enzymes. In the present investigation, the metabolic stability of P57 in human liver microsomes and its interaction with drug metabolizing enzymes (CYP1A2, 2C9, 3A4 and 2D6) were determined. Intestinal transport of P57 was studied in the Caco-2 cell model of intestinal transport and absorption. P57 was metabolically stable in the presence of human liver microsomes. The compound inhibited CYP3A4 activity with an IC 50 value of 45 μM, whereas the activity of CYP 1A2, 2C9 and 2D6 was not inhibited. In the Caco-2 model, P57 exhibited a higher transport in the secretory direction than in the absorptive direction with efflux ratios of 3.1 and 3.8 at 100 and 200 μM, respectively. The efflux was inhibited by selective inhibitors of multidrug resistance associated proteins MRP1/MRP2 (MK-571) and P-gp (verapamil). In conclusion, intestinal transport of P57 was mediated by P-gp and MRP transporters. The compound was metabolically stable and showed weak inhibition of CYP 3A4. Caco-2:human colonic adenocarcinoma CYP:cytochrome P450 H. gordonii: Hoodia gordoniiLy:Lucifer yellow MRP:multidrug resistance-associated protein P57AS3:P57 Papp:apparent permeability P-gp:P-glycoprotein TEER:transepithelial electrical resistance
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new oxypregnane glycosides from appetite suppressant herbal supplement Hoodia gordonii
Steroids, 2007Co-Authors: Rahul S Pawar, Bharathi Avula, Yatin J Shukla, Shabana I Khan, Ikhlas A. KhanAbstract:Abstract Hoodigosides A–K ( 1 – 11 ), eleven new oxypregnane glycosides and a previously reported oxypregnane glycoside P57AS3 were isolated from the aerial parts of Hoodia gordonii . The structures of these 12- O -β-tigloyl isoramanone glycosides were determined on the basis of chemical evidence and extensive spectroscopic methods that include one-dimensional and two-dimensional NMR. Cytotoxicity and antioxidant activities of these compounds were tested in cell based assays where they were found to be inactive.
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New oxypregnane glycosides from appetite suppressant herbal supplement Hoodia gordonii.
Steroids, 2007Co-Authors: Rahul S Pawar, Bharathi Avula, Yatin J Shukla, Shabana I Khan, Ikhlas A. KhanAbstract:Hoodigosides A-K (1-11), eleven new oxypregnane glycosides and a previously reported oxypregnane glycoside P57AS3 were isolated from the aerial parts of Hoodia gordonii. The structures of these 12-O-beta-tigloyl isoramanone glycosides were determined on the basis of chemical evidence and extensive spectroscopic methods that include one-dimensional and two-dimensional NMR. Cytotoxicity and antioxidant activities of these compounds were tested in cell based assays where they were found to be inactive.