Synergistic Interactions of Atractylodes lancea Rhizome Compounds in the Treatment of Cholangiocarcinoma | Chapter 7 | Contemporary Research and Perspectives in Biological Science Vol. 3

 

Background: Cholangiocarcinoma (CCA)is the primary type of bile duct cancer with high morbidity and mortality, particularly in patients with advanced stages. Numerous studies have been carried out in efforts to discover effective cancer chemotherapeutic agents from plant sources with low toxicity. Treatment of CCA remains unsatisfactory due to the lack of sensitive and specific diagnostic tools for early detection and effective chemotherapeutics.

Purpose: The primary purpose of this study is to investigate cytotoxic interactions between the three major constituents of the rhizomes of Atractylodeslancea (Thunb)DC., i.e., β-eudesmol (BE), atractylodin (AT), and hinesol (HS) against CCA cell line. 

Methods: The bioactive constituents of AL rhizome under investigation, ie, BE, AT, HS, and 5-FU were purchased from Wako (Wako Ltd., Osaka, Japan). Cytotoxic activities against the human CCA cells CL-6 of the dual (BE:AT, BE:HS, and AT:HS) and triple (BE:AT:HS) combinations were evaluated using the assay. The cytotoxic interaction of each dual combination was assessed at five concentration ratios (10:0, 7:3, 5:5, 3:7, and 0:10) using isobologram analysis. The fractional inhibitory concentration index of each combination pair (representing combination scores) and the sum FIC of five distinctive ratios were calculated as the ratio of IC50 of the combination and that of each compound alone. For triple combination, the concentration ratio used in the experiment was 1:1.5:2.5(BE:AT:HS), and analysis of the interaction was performed using polygonogram analysis at the IC50 and IC90 concentrations (concentration that inhibits cell growth by 50% and 90%, respectively).

Results: The study was the first that confirmed the cytotoxic synergistic interaction of the three major compounds from AL rhizome on the human CCA cell line CL-6. The BE:AT combination produced the additive effect with a sum FIC (fractional inhibitory concentration) of 0.967±0.02 (mean±SD). The BE:HS and AT:HS combinations produced a synergistic effect with sum FICs of 0.685±0.08 and 0.767±0.09, respectively. The mixture of the three compounds produced synergistic interaction with CI (combination index) values of 0.519±0.10 and 0.65±0.17 (mean±SD) at the IC₅₀ and IC₉₀ concentration levels, respectively. 

Conclusion: The multi-ingredient characteristics of the plant extract would be expected to optimize therapy regarding both efficacy (synergistic anti-CCA activity) and tolerability (buffering effect). Results obtained would guide further development of AL as a potential anti-CCA chemotherapeutics concerning the appropriate pharmaceutical dosage form.

 

Author (s) Details

Pongsakorn Martviset
Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand and Faculty of Medical Technology, Rangsit University, Pathumthani 12000, Thailand.

 

Kesara Na-Bangchang
Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand, Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand and Drug Discovery and Development Center, Thammasat University, Pathumthani 12121, Thailand.

 

Please see the book here:- https://doi.org/10.9734/bpi/crpbs/v3/2408

Synergistic Interactions of Atractylodes lancea Rhizome Compounds in the Treatment of Cholangiocarcinoma | Chapter 7 | Contemporary Research and Perspectives in Biological Science Vol. 3

Background: Cholangiocarcinoma (CCA)is the primary type of bile duct cancer with high morbidity and mortality, particularly in patients with advanced stages. Numerous studies have been carried out in efforts to discover effective cancer chemotherapeutic agents from plant sources with low toxicity. Treatment of CCA remains unsatisfactory due to the lack of sensitive and specific diagnostic tools for early detection and effective chemotherapeutics.

Purpose: The primary purpose of this study is to investigate cytotoxic interactions between the three major constituents of the rhizomes of Atractylodeslancea (Thunb)DC., i.e., β-eudesmol (BE), atractylodin (AT), and hinesol (HS) against CCA cell line. 

Methods: The bioactive constituents of AL rhizome under investigation, ie, BE, AT, HS, and 5-FU were purchased from Wako (Wako Ltd., Osaka, Japan). Cytotoxic activities against the human CCA cells CL-6 of the dual (BE:AT, BE:HS, and AT:HS) and triple (BE:AT:HS) combinations were evaluated using the assay. The cytotoxic interaction of each dual combination was assessed at five concentration ratios (10:0, 7:3, 5:5, 3:7, and 0:10) using isobologram analysis. The fractional inhibitory concentration index of each combination pair (representing combination scores) and the sum FIC of five distinctive ratios were calculated as the ratio of IC50 of the combination and that of each compound alone. For triple combination, the concentration ratio used in the experiment was 1:1.5:2.5(BE:AT:HS), and analysis of the interaction was performed using polygonogram analysis at the IC50 and IC90 concentrations (concentration that inhibits cell growth by 50% and 90%, respectively).

Results: The study was the first that confirmed the cytotoxic synergistic interaction of the three major compounds from AL rhizome on the human CCA cell line CL-6. The BE:AT combination produced the additive effect with a sum FIC (fractional inhibitory concentration) of 0.967±0.02 (mean±SD). The BE:HS and AT:HS combinations produced a synergistic effect with sum FICs of 0.685±0.08 and 0.767±0.09, respectively. The mixture of the three compounds produced synergistic interaction with CI (combination index) values of 0.519±0.10 and 0.65±0.17 (mean±SD) at the IC₅₀ and IC₉₀ concentration levels, respectively. 

Conclusion: The multi-ingredient characteristics of the plant extract would be expected to optimize therapy regarding both efficacy (synergistic anti-CCA activity) and tolerability (buffering effect). Results obtained would guide further development of AL as a potential anti-CCA chemotherapeutics concerning the appropriate pharmaceutical dosage form.

 

Author (s) Details

Pongsakorn Martviset
Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand and Faculty of Medical Technology, Rangsit University, Pathumthani 12000, Thailand.

 

Kesara Na-Bangchang
Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand, Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand and Drug Discovery and Development Center, Thammasat University, Pathumthani 12121, Thailand.

 

Please see the book here:- https://doi.org/10.9734/bpi/crpbs/v3/2408

Modulatory Effects Atractylodes lancea on CYP1A2 and CYP3A1, Pharmacokinetics and Biodistribution | Chapter 7 | Novel Aspects on Pharmaceutical Research Vol. 4

 The study proposed to investigate the modulatory belongings of Atractylodes lancea (Thunb.) DC. (A. lancea: AL), a promising candidate for medicating cholangiocarcinoma, on cytochrome P450 (CYP450) 1A2 AND 3A1, pharmacokinetics and biodistribution in animals. Herbal cure is becoming more used to enhance general strength and well-being, and it is still used alone for particular health questions or with up-to-date medicine. To investigate CYP1A2 and CYP3A1 modulatory actions following long-term uncovering, rats of both genders taken oral doses of the formulated AL at 1,000 (depressed dose), 3,000 (medium prescription), and 5,000 (high lot) mg/kg body weight regularly for 12 months. For short-term belongings, male rats were orally administered the planned AL at 5,000 mg/kg body burden daily for 1, 7, 14 and 21 days. The pharmacokinetic study was administered in male rats after administration of the planned AL at the dose of 5,000 mg/kg bulk weight constantly for nine months. Due to the poor solubility of ATD, which power affect the bioavailability of the compound, the bioavailability and biodistribution of the polylactic-co-glycolic acid nanoparticles of ATD (ATD-PLGA-NPs) were examined in mouse liver utilizing matrix-assisted ray of light desorption ionization-imaging bulk spectrometer (MALDI-IMS). The biodistribution study was conducted in a male rodent receiving ATD-PLGA-NPs at the equivalent dose to ATD of 100 mg/kg bulk weight. The extreme dose of formulated AL created an inducing effect on CYP1A2 but an inhibitory effect on CYP3A1 ventures in male rats. The low prescription, however, did not prevent or induce the projects of both enzymes in male and female rats. The current examination of CYP450 modulatory activities was part of a big study to evaluate never-ending toxicity (long-term uncovering) and to identify the metabolic pathway (temporary exposure) of the planned AL. ATD reached a maximum plasma aggregation (Cmax) of 359.73 ng/mL at 3 h (tmax). Mean residence opportunity (MRT) and terminal phase removal half-life (t1/2z) were 3.03 and 0.56 h, respectively. The extent of biodistribution of ATD in rodent livers taking ATD-PLGA-NPs was 5-fold of that receiving free ATD. In order to avoid potential herb-drug interactions afterwards prolonged use, dispassionate use of low-shot AL should be taken into concern. ATD-PLGA-NPs is a possible drug transmittal system for the treatment of cholangiocarcinoma.

Author(s) Details:

Kesara Na-Bangchang,
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani, Thailand, Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani, Thailand and Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University (Rangsit Campus), Pathumthani, Thailand.

Tullayakorn Plengsuriyakarn,
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani, Thailand.

Please see the link here: https://stm.bookpi.org/NAPR-V4/article/view/11005

Immunomodulatory Activities of Atractylodes lancea (Thunb.) DC | Chapter 5 | Current Practice in Medical Science Vol. 7

 

 In vitro and In vivo research have shown that Atractylodes lancea (Thunb) DC. (AL) and its bioactive parts - eudesmol and atractylodin could be utilized to treat cholangiocarcinoma. The review meant to assess the immunomodulatory action of AL in human subjects. The modulatory impacts of AL and -eudesmol and atractylodin on TNFα and IL6 articulation in PBMCs were estimated utilizing continuous PCR. Blood tests were taken from 48 sound subjects after they were given a solitary or various dosages of the normalized AL remove case definition or a fake treatment. Serum cytokine profiles, lymphocyte subpopulations (B lymphocytes, CD8+ cytotoxic T lymphocytes, CD4+ T-partner lymphocytes, and NK cells), and cytotoxic action of PBMCs against the cholangiocarcinoma cell line CL-6 were assessed utilizing cytometric dab exhibit (CBA) with stream cytometry examination. AL separate at practically all focuses essentially hindered both TNFα and IL6 articulation in Con A-interceded irritation in PBMCs. Just IL6 articulation was altogether decreased by β-Eudesmol at all dosages. At the most reduced portion, atractylodin impressively diminished the statement of the two cytokines, though at the most elevated fixation, just IL6 articulation was altogether restrained. The organization of AL at a solitary oral portion of 1,000 mg seemed to diminish IFN and IL10 and increment B cells, while fundamentally expanding NK and CD4+ and CD8+ cells. At 24 hours after measurements, there was a pattern of expanding cytotoxic action of PBMCs (comparative with fake treatment). At 24 hours after measurement, AL at progressive portions of 1,000 mg for 21 days would in general decrease the creation of all cytokines while fundamentally stifling IL17A creation. By 24 hours, there was a pattern of expanded cytotoxic action in PBMCs, yet this pattern halted at 48 hours. The discoveries support AL's immunomodulatory properties in people. This action, along with AL's immediate impact in setting off apoptosis in cholangiocarcinoma cells, suggests that it could play a part in CCA guideline.

Author(s) Details:

Inthuon Kulma,
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.

Luxsana Panrit,
Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.

Tullayakorn Plengsuriyakarn,
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.

Wanna Chaijaroenkul,
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.

Siriprapa Warathumpitak,
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand and  Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.

Kesara Na-Bangchang,
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand and  Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.

Please see the link here: https://stm.bookpi.org/CPMS-V7/article/view/7836