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3. Invivo evaluation of Andrographis paniculata and Boesenbergia rotunda extract activity against SARS-CoV-2 Delta variant in Golden Syrian hamsters: Potential herbal alternative for COVID-19 treatment

Author

Kongsomros, Supasek, Boonyarattanasoonthorn, Tussapon, Phongphaew, Wallaya, Kasorndorkbua, Chaiyan, Sunyakumthorn, Piyanate, Im-Erbsin, Rawiwan, Lugo-Roman, Luis A., Kongratanapasert, Teetat, Paha, Jiraporn, Manopwisedjaroen, Suwimon, Kwankhao, Pakakrong, Supannapan, Kittitach, Ngamkhae, Nittaya, Srimongkolpithak, Nitipol, Vivithanaporn, Pornpun, Hongeng, Suradej, Thitithanyanont, Arunee, and Khemawoot, Phisit

Published
2024
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7. Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs.

Author

Songvuta, Phanit, Boonyarattanasoonthorn, Tussapon, Nuengchamnong, Nitra, Junsaid, Thammaporn, Kongratanapasert, Teetat, Supannapan, Kittitach, and Khemawoot, Phisit

Subjects
ANDROGRAPHIS paniculata, BEAGLE (Dog breed), BIOAVAILABILITY, SODIUM dodecyl sulfate, PHARMACOKINETICS, CYCLODEXTRINS
Abstract

Context: the therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility. Objective: this work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer. Materials and methods: Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) β-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. all groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days. Results: thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w β-cyclodextrin or 1% w/w sDs, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces. Conclusion: the combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Invivoevaluation of Andrographis paniculataand Boesenbergia rotundaextract activity against SARS-CoV-2 Delta variant in Golden Syrian hamsters: Potential herbal alternative for COVID-19 treatment

Author

Kongsomros, Supasek, Boonyarattanasoonthorn, Tussapon, Phongphaew, Wallaya, Kasorndorkbua, Chaiyan, Sunyakumthorn, Piyanate, Im-Erbsin, Rawiwan, Lugo-Roman, Luis A., Kongratanapasert, Teetat, Paha, Jiraporn, Manopwisedjaroen, Suwimon, Kwankhao, Pakakrong, Supannapan, Kittitach, Ngamkhae, Nittaya, Srimongkolpithak, Nitipol, Vivithanaporn, Pornpun, Hongeng, Suradej, Thitithanyanont, Arunee, and Khemawoot, Phisit

Abstract

The ongoing COVID-19 pandemic has triggered extensive research, mainly focused on identifying effective therapeutic agents, specifically those targeting highly pathogenic SARS-CoV-2 variants. This study aimed to investigate the in vivoantiviral efficacy and anti-inflammatory activity of herbal extracts derived from Andrographis paniculataand Boesenbergia rotunda, using a Golden Syrian hamster model infected with Delta, a representative variant associated with severe COVID-19. Hamsters were intranasally inoculated with the SARS-CoV-2 Delta variant and orally administered either vehicle control, B. rotunda, or A.paniculataextract at a dosage of 1000 mg/kg/day. Euthanasia was conducted on days 1, 3, and 7 post-inoculation, with 4 animals per group. The results demonstrated that oral administration of A. paniculataextract significantly alleviated both lethality and infection severity compared with the vehicle control and B. rotundaextract. However, neither extract exhibited direct antiviral activity in terms of reducing viral load in the lungs. Nonetheless, A. paniculataextract treatment significantly reduced IL-6 protein levels in the lung tissue (7278 ± 868.4 pg/g tissue) compared to the control (12,495 ± 1118 pg/g tissue), indicating there was a decrease in local inflammation. This finding is evidenced by the ability of A. paniculataextract to reduce histological lesions in the lungs of infected hamsters. Furthermore, both extracts significantly decreased IL-6 and IP-10 mRNA expression in peripheral blood mononuclear cells of infected hamsters compared to the control group, suggesting systemic anti-inflammatory effects occurred. In conclusion, A. paniculataextract's potential therapeutic application for SARS-CoV-2 arises from its observed capacity to lessen inflammatory cytokine concentrations and mitigate lung pathology.

Published
2024
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11. Oral Bioavailability, Tissue Distribution, Metabolism, and Excretion of Panduratin A from Boesenbergia rotunda Extract in Healthy Rats

Author

Kongratanapasert,Teetat, Boonyarattanasoonthorn,Tussapon, Supannapan,Kittitach, Hongeng,Suradej, Khemawoot,Phisit, Kongratanapasert,Teetat, Boonyarattanasoonthorn,Tussapon, Supannapan,Kittitach, Hongeng,Suradej, and Khemawoot,Phisit

Abstract

Teetat Kongratanapasert,1,2 Tussapon Boonyarattanasoonthorn,3 Kittitach Supannapan,4 Suradej Hongeng,5 Phisit Khemawoot1 1Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn, Thailand; 2Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Chulalongkorn University Laboratory Animal Center, Chulalongkorn University, Bangkok, Thailand; 4Chao Phraya Abhaibhubejhr Hospital Foundation, Prachinburi, Thailand; 5Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Phisit Khemawoot, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Tel/Fax +66 28395161, Email phisit.khe@mahidol.ac.thBackground: Our previous studies in vitro and in vivo have shown anti-severe acute respiratory syndrome coronavirus 2 activity of fingerroot extract (Boesenbergia rotunda) and its phytochemical panduratin A.Aim of Study: Therefore, the objective of this study was to determine the pharmacokinetic profiles of panduratin A, as a pure compound and in fingerroot extract, in rats.Materials and Methods: Male rats were randomly divided into four groups. Rats underwent intravenous administration of 4.5 mg/kg panduratin A, a single oral administration of 45 mg/kg panduratin A, or a multiple oral administration of 45 mg/kg panduratin A-consisted fingerroot extract for 7 consecutive days. The concentrations of panduratin A in plasma, tissues, and excreta were measured by using LCMS with a validated method.Results: The rats showed no change in health status after receiving all test preparations. The absolute oral bioavailability of panduratin A administered as pure panduratin A and fingerroot extract were approximately 9% and 6%, respectively. The peak concentrations for the single oral doses of 45 mg/kg panduratin A and fingerroot extract, were 4833 ± 659 and 3269 Â

Published
2024

20. Absolute oral bioavailability and possible metabolic pathway of panduratin A from Boesenbergia rotunda extract in beagle dogs

Author

Boonyarattanasoonthorn, Tussapon, Kongratanapasert, Teetat, Jiso, Apisada, Techapichetvanich, Pinnakarn, Nuengchamnong, Nitra, Supannapan, Kittitach, Kijtawornrat, Anusak, and Khemawoot, Phisit

Subjects
Pharmacology, Complementary and alternative medicine, Drug Discovery, Pharmaceutical Science, Molecular Medicine, General Medicine
Abstract

Attempts are ongoing to develop medications to fight against the COVID-19 pandemic. Our previous study revealed the in vitro anti-SARS-CoV-2 activity of fingerroot [Boesenbergia rotunda (L.) Mansf. (Zingiberaceae)] and its phytochemical, panduratin A. To investigate the pharmacokinetic profiles of panduratin A as a pure compound and in a fingerroot extract formulation in beagle dogs. A total of 12 healthy dogs were randomly divided into three groups, a single dose of 1 mg/kg panduratin A by intravenous and multiple doses of 5 and 10 mg/kg panduratin A fingerroot extract formulation by oral administration for seven consecutive days. The plasma concentration of panduratin A was determined by LCMS. The peak concentrations of a single dose of 5 and 10 mg/kg panduratin A fingerroot extract formulation were 12,416 ± 2,326 and 26,319 ± 8,221 µg/L, respectively. Increasing the oral dose of fingerroot extract formulation, equivalent to panduratin A 5–10 mg/kg, showed dose proportionality, with an approximately 2-fold increase in Cmax and AUC. The absolute oral bioavailability of panduratin A in the fingerroot extract formulation was approximately 7–9%. The majority of panduratin A was biotransformed into several products via oxidation and glucuronidation, and predominantly excreted via the faecal route. The oral formulation of fingerroot extract was safe in beagle dogs, and increasing dose showed dose proportionality in terms of the systemic exposure of panduratin A. This information will support the phytopharmaceutical product development of fingerroot extract against the COVID-19 pandemic.

Published
2023
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21. High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents

Author

Kanjanasirirat, Phongthon, Suksatu, Ampa, Manopwisedjaroen, Suwimon, Munyoo, Bamroong, Tuchinda, Patoomratana, Jearawuttanakul, Kedchin, Seemakhan, Sawinee, Charoensutthivarakul, Sitthivut, Wongtrakoongate, Patompon, Rangkasenee, Noppawan, Pitiporn, Supaporn, Waranuch, Neti, Chabang, Napason, Khemawoot, Phisit, Sa-ngiamsuntorn, Khanit, Pewkliang, Yongyut, Thongsri, Piyanoot, Chutipongtanate, Somchai, Hongeng, Suradej, Borwornpinyo, Suparerk, and Thitithanyanont, Arunee

Published
2020
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23. Pharmacological Activities of Fingerroot Extract and Its Phytoconstituents Against SARS-CoV-2 Infection in Golden Syrian Hamsters

Author

Kongratanapasert,Teetat, Kongsomros,Supasek, Arya,Nlin, Sutummaporn,Kripitch, Wiriyarat,Witthawat, Akkhawattanangkul,Yada, Boonyarattanasoonthorn,Tussapon, Asavapanumas,Nithi, Kanjanasirirat,Phongthon, Suksatu,Ampa, Sa-ngiamsuntorn,Khanit, Borwornpinyo,Suparerk, Vivithanaporn,Pornpun, Chutipongtanate,Somchai, Hongeng,Suradej, Ongphiphadhanakul,Boonsong, Thitithanyanont,Arunee, Khemawoot,Phisit, Sritara,Piyamitr, Kongratanapasert,Teetat, Kongsomros,Supasek, Arya,Nlin, Sutummaporn,Kripitch, Wiriyarat,Witthawat, Akkhawattanangkul,Yada, Boonyarattanasoonthorn,Tussapon, Asavapanumas,Nithi, Kanjanasirirat,Phongthon, Suksatu,Ampa, Sa-ngiamsuntorn,Khanit, Borwornpinyo,Suparerk, Vivithanaporn,Pornpun, Chutipongtanate,Somchai, Hongeng,Suradej, Ongphiphadhanakul,Boonsong, Thitithanyanont,Arunee, Khemawoot,Phisit, and Sritara,Piyamitr

Abstract

Teetat Kongratanapasert,1,* Supasek Kongsomros,2,5,* Nlin Arya,3 Kripitch Sutummaporn,3 Witthawat Wiriyarat,3 Yada Akkhawattanangkul,4 Tussapon Boonyarattanasoonthorn,5 Nithi Asavapanumas,5 Phongthon Kanjanasirirat,6 Ampa Suksatu,2 Khanit Sa-ngiamsuntorn,7 Suparerk Borwornpinyo,6,8 Pornpun Vivithanaporn,5 Somchai Chutipongtanate,5,9 Suradej Hongeng,6,9 Boonsong Ongphiphadhanakul,10 Arunee Thitithanyanont,2 Phisit Khemawoot,5 Piyamitr Sritara10 1Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand; 2Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand; 3Department of Preclinic and Applied Animal Science, Faculty of Veterinary Science, Mahidol University, Nakhonpathom, 73170, Thailand; 4Department of Clinical Medicine and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhonpathom, 73170, Thailand; 5Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn, 10540, Thailand; 6Excellence Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; 7Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand; 8Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; 9Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand; 10Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand*These authors contributed equally to this workCorrespondence: Phisit Khemawoot, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, 10540, Thailand, Tel/Fax +66 28395161, Email phisit.khe@mahidol.ac.thBackground: The outbreak of COVID-19 has led to the suffering of people around the world, with an inaccessibili

Published
2023

25. Pharmacokinetics of Curcumin Diethyl Disuccinate, a Prodrug of Curcumin, in Wistar Rats

Author

Bangphumi, Kunan, Kittiviriyakul, Chuleeporn, Towiwat, Pasarapa, Rojsitthisak, Pornchai, and Khemawoot, Phisit

Abstract

Curcumin is the major bioactive component of turmeric, but has poor oral bioavailability that limits its clinical applications. To improve the in vitro solubility and alkaline stability, we developed a prodrug of curcumin by succinylation to obtain curcumin diethyl disuccinate, with the goal of improving the oral bioavailability of curcumin. The in vivo pharmacokinetic profile of curcumin diethyl disuccinate was compared with that of curcumin in male Wistar rats. Doses of curcumin 20 mg/kg intravenous or 40 mg/kg oral were used as standard regimens for comparison with the prodrug at equivalent doses in healthy adult rats. Blood, tissues, urine, and faeces were collected from time zero to 48 h after dosing to determine the prodrug level, curcumin level and a major metabolite by liquid chromatography-tandem spectrometry. The absolute oral bioavailability of curcumin diethyl disuccinate was not significantly improved compared with curcumin, with both compounds having oral bioavailability of curcumin less than 1 %. The major metabolic pathway of the prodrug was rapid hydrolysis to obtain curcumin, followed by glucuronidation. Interestingly, curcumin diethyl disuccinate gave superior tissue distribution with higher tissue to plasma ratio of curcumin and curcumin glucuronide in several organs after intravenous dosing at 1 and 4 h. The primary elimination route of curcumin glucuronide occurred via biliary and faecal excretion, with evidence of an entry into the enterohepatic circulation. Curcumin diethyl disuccinate did not significantly improve the oral bioavailability of curcumin due to first pass metabolism in the gastrointestinal tract. Further studies on reduction of first pass metabolism are required to optimise delivery of curcumin using a prodrug approach.

Published
2024
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28. Pharmacological Activities of Fingerroot Extract and Its Phytoconstituents Against SARS-CoV-2 Infection in Golden Syrian Hamsters [Corrigendum]

Author

Kongratanapasert, Teetat, primary, Kongsomros, Supasek, additional, Arya, Nlin, additional, Sutummaporn, Kripitch, additional, Wiriyarat, Witthawat, additional, Akkhawattanangkul, Yada, additional, Boonyarattanasoonthorn, Tussapon, additional, Asavapanumas, Nithi, additional, Kanjanasirirat, Phongthon, additional, Suksatu, Ampa, additional, Sa-ngiamsuntorn, Khanit, additional, Borwornpinyo, Suparerk, additional, Vivithanaporn, Pornpun, additional, Chutipongtanate, Somchai, additional, Hongeng, Suradej, additional, Ongphiphadhanakul, Boonsong, additional, Thitithanyanont, Arunee, additional, Khemawoot, Phisit, additional, and Sritara, Piyamitr, additional

Published
2023
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34. Dose-dependent risk of neutropenia after 7-day courses of artesunate monotherapy in Cambodian patients with acute plasmodium falciparum malaria

Author

Bethell, Delia, Se, Youry, Lon, Chanthap, Socheat, Duong, Saunders, David, Teja-Isavadharm, Paktiya, Khemawoot, Phisit, Darapiseth, Sea, Lin, Jessica, Sriwichai, Sabaithip, Kuntawungin, Worachet, Surasri, Sittidech, Lee, Sue J., Sarim, Ses, Tyner, Stuart, and Fukuda, Mark M.

Subjects
Neutropenia -- Risk factors, Malaria -- Drug therapy, Health, Health care industry
Published
2010

35. Anti-SARS-CoV-2 Activity of Andrographis paniculata Extract and Its Major Component Andrographolide in Human Lung Epithelial Cells and Cytotoxicity Evaluation in Major Organ Cell Representatives

Author

Sa-ngiamsuntorn, Khanit, primary, Suksatu, Ampa, additional, Pewkliang, Yongyut, additional, Thongsri, Piyanoot, additional, Kanjanasirirat, Phongthon, additional, Manopwisedjaroen, Suwimon, additional, Charoensutthivarakul, Sitthivut, additional, Wongtrakoongate, Patompon, additional, Pitiporn, Supaporn, additional, Chaopreecha, Jarinya, additional, Kongsomros, Supasek, additional, Jearawuttanakul, Kedchin, additional, Wannalo, Warawuth, additional, Khemawoot, Phisit, additional, Chutipongtanate, Somchai, additional, Borwornpinyo, Suparerk, additional, Thitithanyanont, Arunee, additional, and Hongeng, Suradej, additional

Published
2021
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38. Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives

Author

Sa-ngiamsuntorn, Khanit, primary, Suksatu, Ampa, additional, Pewkliang, Yongyut, additional, Thongsri, Piyanoot, additional, Kanjanasirirat, Phongthon, additional, Manopwisedjaroen, Suwimon, additional, Charoensutthivarakul, Sitthivut, additional, Wongtrakoongate, Patompon, additional, Pitiporn, Supaporn, additional, Khemawoot, Phisit, additional, Chutipongtanate, Somchai, additional, Borwornpinyo, Suparerk, additional, Thitithanyanont, Arunee, additional, and Hongeng, Suradej, additional

Published
2020
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39. 15788 The standardized extract of Centella asiatica, ECa 233, enhances post-laser resurfacing wound healing on the face: A split-face, double-blind, randomized, placebo-controlled trial

Author

Damkerngsuntorn, Wilawan, primary, Rerknimitr, Pawinee, additional, Asawanonda, Pravit, additional, Panchaprateep, Ratchathorn, additional, Kumtornrut, Chanat, additional, Kerr, Stephen, additional, Tangkijngamvong, Natsinee, additional, and Khemawoot, Phisit, additional

Published
2020
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41. High-Content Screening of Thai Medicinal Plants Reveals Boesenbergia rotunda Extract and its Component Panduratin A as Anti-SARS-CoV-2 Agents

Author

Kanjanasirirat, Phongthon, primary, Suksatu, Ampa, additional, Manopwisedjaroen, Suwimon, additional, Munyoo, Bamroong, additional, Tuchinda, Patoomratana, additional, Jearawuttanakul, Kedchin, additional, Seemakhan, Sawinee, additional, Charoensutthivarakul, Sitthivut, additional, Wongtrakoongate, Patompon, additional, Rangkasenee, Noppawan, additional, Pitiporn, Supaporn, additional, Waranuch, Neti, additional, Chabang, Napason, additional, Khemawoot, Phisit, additional, Chutipongtanate, Somchai, additional, Hongeng, Suradej, additional, Borwornpinyo, Suparerk, additional, and Thitithanyanont, Arunee, additional

Published
2020
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42. The Effects of a Standardized Extract of Centella asiatica on Postlaser Resurfacing Wound Healing on the Face: A Split-Face, Double-Blind, Randomized, Placebo-Controlled Trial

Author

Damkerngsuntorn, Wilawan, primary, Rerknimitr, Pawinee, additional, Panchaprateep, Ratchathorn, additional, Tangkijngamvong, Natsinee, additional, Kumtornrut, Chanat, additional, Kerr, Stephen J., additional, Asawanonda, Pravit, additional, Tantisira, Mayuree H., additional, and Khemawoot, Phisit, additional

Published
2020
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50. Anti-SARS-CoV-2 Activity of Extract and Its Major Component Andrographolide in Human Lung Epithelial Cells and Cytotoxicity Evaluation in Major Organ Cell Representatives.

Author

Sa-ngiamsuntorn, Khanit, Suksatu, Ampa, Pewkliang, Yongyut, Thongsri, Piyanoot, Kanjanasirirat, Phongthon, Manopwisedjaroen, Suwimon, Charoensutthivarakul, Sitthivut, Wongtrakoongate, Patompon, Pitiporn, Supaporn, Chaopreecha, Jarinya, Kongsomros, Supasek, Jearawuttanakul, Kedchin, Wannalo, Warawuth, Khemawoot, Phisit, Chutipongtanate, Somchai, Borwornpinyo, Suparerk, Thitithanyanont, Arunee, and Hongeng, Suradej

Published
2021
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