Publications by authors named "Intouch Sakpakdeejaroen"

13 Publications

  • Page 1 of 1

Bactericidal Effect and Anti-Inflammatory Activity of Heartwood Extract.

ScientificWorldJournal 2020 13;2020:1653180. Epub 2020 Jul 13.

Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Khlong Nueng, Pathumthani 12120, Thailand.

Natural products are used as alternative drugs in traditional medicine to treat infection and inflammation and relieve pain. Heartwood of Craib has been investigated as an ingredient in Thai traditional medicine for anti-HIV protease, but there is no report on its antibacterial and anti-inflammatory activities. The objectives of this study were to investigate the anti-inflammatory and antibacterial activities, time-kill profile, and main active constituents of an ethanolic extract of heartwood. The study followed the generally accepted experimental design. All tests were investigated in triplicate. The heartwood of was extracted by maceration with 95% EtOH. The antibacterial activity of the extract and its chemical constituents were determined by their MIC values using resazurin as an indicator. Time-kill profile was determined at 0, 2, 4, 6, 8, 10, 12, and 24 hrs and expressed as log CFU/mL. The anti-inflammatory activity of the extract and its chemical components was investigated by their inhibiting effect on IL-6 and TNF- production by ELISA. The ethanolic extract was analyzed for its chemical constituents by HPLC technique. The ethanolic extract showed both dose- and time-dependent bactericidal effects against , methicillin-resistance , , , , Typhi, Typhimurium, , and with MIC values of 312.5, 312.5, 312.5, 1,250, 2,500, 625, 625, 2,500, and 625 g/mL, respectively. It showed an inhibiting effect on IL-6 production at concentrations of 12.5 to 100 g/mL. The main active chemical constituent of was piceatannol that showed antibacterial activity against all test bacteria except . showed a broad spectrum of antibacterial activity against both Gram-negative and Gram-positive bacteria. Piceatannol and resveratrol from the plant strongly inhibited IL-6 production. Based on these results, we concluded that the ethanolic extract of showed both an antibacterial activity and inhibition of IL-6. Piceatannol is the active constituent of the extract and showed anti-inflammatory and antibacterial activities against Gram-negative and Gram-positive bacteria.
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http://dx.doi.org/10.1155/2020/1653180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374238PMC
July 2020

Anti-Tumor Activity of Intravenously Administered Plumbagin Entrapped in Targeted Nanoparticles.

J Biomed Nanotechnol 2020 Jan;16(1):85-100

Plumbagin, a natural naphthoquinone from the officinal leadwort, has recently been shown to exert promising anti-cancer effects. However, its therapeutic use is hampered by its failure to specifically reach tumors after intravenous administration, without secondary effects on normal tissues. Its poor solubility in water and rapid elimination following administration further limit its potential use. We hypothesize that the entrapment of plumbagin within PEGylated PLGA nanoparticles conjugated with transferrin, whose receptors are overexpressed on many types of cancer cells, could lead to a selective delivery of the drug to tumors following intravenous administration and enhance its chemotherapeutic effects. The objectives of this study were therefore to prepare and characterize transferrin-conjugated, PEGylated PLGA nanoparticles entrapping plumbagin, and to assess their anti-cancer efficacy as well as in tumor-bearing mice. The intravenous administration of transferrin-conjugated PEGylated PLGA nanoparticles resulted in the complete suppression of 10% of B16-F10 tumors and regression of 30% of the tumors, with improvement of the animal survival compared to controls. The treatment was well tolerated by the animals. Transferrin-bearing PEGylated PLGA nanoparticles entrapping plumbagin are therefore highly promising therapeutic systems, able to lead to tumor regression and even suppression after intravenous administration without visible toxicity.
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http://dx.doi.org/10.1166/jbn.2020.2874DOI Listing
January 2020

Transferrin-bearing liposomes entrapping plumbagin for targeted cancer therapy.

J Interdiscip Nanomed 2019 Jun 26;4(2):54-71. Epub 2019 Jun 26.

Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde 161 Cathedral Street Glasgow G4 0RE UK.

The therapeutic potential of plumbagin, a naphthoquinone extracted from the officinal leadwort with anticancer properties, is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use in clinic is further limited by its poor aqueous solubility, its spontaneous sublimation, and its rapid elimination . We hypothesize that the entrapment of plumbagin within liposomes grafted with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumours after intravenous administration. The objectives of this study were therefore to prepare and characterize transferrin-targeted liposomes entrapping plumbagin and to evaluate their therapeutic efficacy and . The entrapment of plumbagin in transferrin-bearing liposomes led to an increase in plumbagin uptake by cancer cells and improved antiproliferative efficacy and apoptosis activity in B16-F10, A431, and T98G cell lines compared with that observed with the drug solution. the intravenous injection of transferrin-bearing liposomes entrapping plumbagin led to tumour suppression for 10% of B16-F10 tumours and tumour regression for a further 10% of the tumours. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any signs of toxicity. Transferrin-bearing liposomes entrapping plumbagin are therefore highly promising therapeutic systems that should be further optimized as a therapeutic tool for cancer treatment.
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http://dx.doi.org/10.1002/jin2.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619241PMC
June 2019

Development of transferrin-bearing vesicles encapsulating aspirin for cancer therapy.

J Liposome Res 2020 Jun 5;30(2):174-181. Epub 2019 Jun 5.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.

Originally developed for the treatment of inflammatory disorders, the non-steroidal anti-inflammatory drug aspirin was shown to have a preventive effect against cancer in the past decades. Most importantly, recent studies suggested that it might also provide a therapeutic benefit in the treatment of cancer . However, this drug failed to specifically reach tumors at a therapeutic concentration following intravenous administration, thus resulting in lack of efficacy on tumors. In this work, we demonstrated that aspirin could be formulated in transferrin-bearing vesicles and that this tumor-targeted formulation could lead to an increase in the anti-proliferative efficacy of the drug in three cancer cell lines . The therapeutic efficacy of aspirin was significantly improved when formulated in transferrin-bearing vesicles, by about 2-fold compared to that of drug solution. These results are promising and support the optimization of this delivery system to further improve its potential as a therapeutic tool in combination with other anti-cancer therapies.
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http://dx.doi.org/10.1080/08982104.2019.1614054DOI Listing
June 2020

Synergistic Genotoxic Effects and Modulation of Cell Cycle by Ginger Ethanolic Extracts in Adjunct to Doxorubicin in Human Lymphocytes In Vitro.

J Med Assoc Thai 2015 Apr;98 Suppl 3:S101-9

Background: Several natural phytochemicals are increasingly used, as an adjunct to chemotherapy, to reduce drug adverse effects. Zingiber officinale rhizome (ginger) product has been reported to be effective against nausea and vomiting in patients receiving emetogenic chemotherapy such as cisplatin/doxorubicin (DXR). In addition, its ethanolic extract of Zingiber officinale rhizome (EEZOR) has been reported to possess anticarcinogenic properties. However, the mechanism for anticancer activity of ginger especially when used in combination with chemotherapy has not well elucidated, one of its possible mechanisms might involve its genotoxicity.

Objective: To investigate genotoxic and cytotoxic potentials of EEZOR alone and EEZOR pretreatments followed by 0.1 mcg/ ml DXR, a genotoxic chemotherapeutic agent in human lymphocytes by sister chromatid exchange (SCE) assay in vitro. The effect on cell cycle kinetics was also explored.

Material And Method: Human lymphocytes were treated with EEZOR alone at 25-500 mcg/ml and EEZOR pretreated at 12.5-200 mcg/ml followed by 0.1 mcg/ml DXR. SCE levels and cell cycle kinetics were evaluated.

Results: EEZOR significantly induced biphasic SCE at 50 and 400 mcg/ml (p < 0.05). However, cytotoxicity manifested at 500 mcg/ml. All EEZOR pretreatments at 12.5, 25, 50, and 100 mcg/ml, except at 200 mcg/ml, prior to DXR, moderately enhanced DXR-induced genotoxicity by 1.3 times (p < 0.05). Both EEZOR alone and EEZOR prior to DXR at certain concentrations delayed cell cycle.

Conclusion: At specific doses, EEZOR could induce genotoxicity and in pretreatments could moderately enhance DXR-induced genotoxicity and delay cell cycle. This finding suggests that dosage use of EEZOR needs to be adjusted for long-term safety. In addition, EEZOR in adjunct to DXM might have potential benefits not only as an emetic agent but also in chemotherapy. Further in vivo animal and human studies to support this evidence is essentially needed.
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April 2015

In vitro enhancement of doxorubicin genotoxic activities and interference with cell cycle delay by Plumbago indica root ethanolic extract in human lymphocytes.

J Med Assoc Thai 2015 Mar;98 Suppl 2:S38-44

Background: Combinations of modern medicines with herbal medicines are being developedfor more effectiveness. Data on the safety and drug-herb interactions are needed to be clarified. Ethanolic extract of Plumbago indica root (EEPIR) is medicinally usedfor cancer treatment in Asian traditional medicine. However its mechanism of action is still inconclusive. Our previous study demonstrated that EEPIR was genotoxic and induced cell cycle delay in human lymphocytes in vitro.

Objective: To investigate genotoxic potency and interference with cell cycle of EEPIR in combination with doxorubicin (DXR), a standard chemotherapeutic agent, in human lymphocytes by in vitro sister chromatid exchange (SCE) assay.

Material And Method: Human lymphocytes were pretreated with EEPIR at 6.25-100 mcg/mlfollowed by DXR (0.1 mcg/ml). SCE levels and cell cycle kinetics were evaluated.

Results: EEPIR pretreatments (6.5-50 mcg/ml) significantly enhanced genetic damage induced by DXR (p<0. 05). Delaying of the cell cycle was detected and related to EEPIR concentration. EEPIR at 100 mcg/ml, on the contrary, did not enhance DXR-induced genotoxicity but tended to lower genotoxicity compared to DXR treatment alone. It significantly delayed cell cycle the most (p<0.05).

Conclusion: EEPIR pretreatments at proper doses enhanced genotoxic damage induced by DXR in human lymphocytes. Delaying cell cycle by EEPIR could lower that potency. Usage of EEPIR, therefore, should be adjusted for safety. Combination of EEPIR with DXR might be usefulfor more efficient cancer treatment with less DXR toxicity. Further in vivo study is needed to support this in vitro evidence.
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March 2015

Biological activities and chemical content of Sung Yod rice bran oil extracted by expression and soxhlet extraction methods.

J Med Assoc Thai 2014 Aug;97 Suppl 8:S125-32

Background: Sung Yod rice is a red-violet pigmented rice and grown in the southern part of Thailand. Its rice bran oil has attracted the attention ofscientists who have described anti-oxidant properties ofsome ingredients in Sung Yod rice bran oil. Normally, extraction methods ofcommercial product from rice bran oil are by expression or soxhlet extraction with hexane. Thus, biological activities of Sung Yod rice bran oil related to health and chemical content ofrice bran oilfrom the two methods should be studied.

Objective: The objectives of this research were to investigate for biological activities and chemical content ofSung Yod rice bran oil obtainedfrom expression or soxhlet extraction method.

Material And Method: Biological activities such as cytotoxic, anti-inflammatory and antioxidant activities were investigated. Sulphorhodamine (SRB) assay was used to test cytotoxic activity against four human cancer cell lines: lung (COR-L23), cervical (HeLa), prostate (PC-3) and breast (MCF-7) and normal human lung cells (MRC-5). The inhibitory effect on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RA W264. 7 cell lines was usedfor the determination of anti-inflammatory effect. DPPH, TEAC and FRAP assay were carried outfor antioxidant activity. Total phenolic compound was determined by Folin-Ciocalteu reagent. y-oryzanol and vitamin E content were determined by HPLC. Sung Yod rice bran oil was produced by expression method (EX) or by soxhlet extraction method using hexane (SXH-I).

Results: The percentage ofyield ofSung Yod rice bran oil by EX and SXH were 2.16 and 15.23 %w/w, respectively. Only EX showed the selective cytotoxicity against prostate cancer cells (PC-3), (IC50 = 52.06±1.60 μg/ml). It also exhibited high inhibitory effects on NO production (IC50 = 30.09 μg/ml). In contrast, SXH had no anti-inflammatory effect and cytotoxic activity against any of the cancer cells. EXshowed higher antioxidant activity determined using DPPH compared to SXH. It also showed higher amount of yoryzanol and vitamin E than that ofSXH (3.09±1.04 and 1.35±1.56 mg % w/w ofextracts, respectively). Yet, SXH exhibited higher antioxidant power determined by FRAP assay and higher total phenolic content compared with EX CONCLUSION: Sung Yod rice bran oil, produced by expression method, had better benefit for health regarding cytotoxicity against prostate cancer cells (PC-3), anti-inflammatory effect and antioxidant (using DPPH) than that produced by soxhlet method extracted with hexane.
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August 2014

Development and validation of RP-HPLC method to determine anti-allergic compound in Thai traditional remedy called Benjalokawichien.

J Med Assoc Thai 2014 Aug;97 Suppl 8:S76-80

Benjalokawichien (BLW) or Ya-Ha-Rak (HR) is a traditional remedy in the Nationaldrug list of herbal medicinal products AD 2012 of Thailand. For traditional use, BLW is used as antipyretic agent. It also has anti-allergic effect, particularly treating allergic rash. The ethanolic extract of BLW exhibited anti-allergic activity via inhibitory effect against a release ofbeta-hexosaminidase in RBL-2H3 cell line. Pectolinarigenin has been identified as the active compound ofBLW extract. In this study, a reversed-phase high performance liquid chromatography (RP-HPLC) method was developed in order to control quality ofpreparation in three aspects such as chemical fingerprint, quantification and stability of the ethanolic extract. The RP-HPLC was performed with a gradient mobile phase composed of 0.1% ortho phosphoric acid and acetronitrile, and peaks were detected at 331 nm. Based on validation results, this analytical method is precise, accurate and stable for quantitative determination ofpectolinarigenin. The amount ofpectolinarigenin in Benjalokawichien extract determined by this method was 18.50 mg/g ofextract. Therefore, this method could be consideredfor quality control ofBLWextract.
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August 2014

Cytotoxic activity against small cell lung cancer cell line and chromatographic fingerprinting of six isolated compounds from the ethanolic extract of Benjakul.

J Med Assoc Thai 2014 Aug;97 Suppl 8:S70-5

Background: Benjakul, a Thai traditional herbal preparation, comnprises five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has widely been used to treat cancer patients in folk medicine in Thailand. Benjakul extract, and its isolated compounds should be investigated for cytotoxic activity and analysis isolated compounds from chemical fingerprinting.

Objective: To study cytotoxicity ofBenjakul extract and its isolatedpure compounds against human small cell lung cancer cell line (NCI-HI 688) and in normal human lungfibroblast cell line (MRC-5) and analysis the content ofisolated compounds for quality control of Benjakul extract.

Material And Method: Bioassay-guided fractionation was used for isolated active compounds from ethanolic extract of Benjakul. Cytotoxic activity was carried using the SRB assay. HPLC method was applied to analyze six isolated compound contentfrom Benjakul extract.

Results: The ethanolic extract ofBenjakul showed cytotoxicity against NCI-H1688 with IC50 value = 36.15±4.35 μg/ml. Hexane fraction as semi-separation by VLC showed the best cytotoxic activity (21.1 7±7.42 μg/ml). Six isolated compounds were identified as myristicin, plumbagin, methyl piperate, 6-shogaol, 6-gingerol and piperine. Plumbagin exhibited the highest cytotoxic activity and 6-shogaol was the second most effective cytotoxic constituent (IC50 values = 1.41±0.01 and 6.45±0.19 μg/ml, respectively). Piperine showed the highest content in both ofHPLC analysis and column chromatography separation.

Conclusion: Benjakul extract exhibited cytotoxicity against NCI-HI 688. Plumbagin and 6-shogaol are bioactive markers for cytotoxicity against this small cell lung cancer cell line. Chromatographic fingerprinting can be used to analyze six cytotoxic compounds isolatedfrom the ethanolic extract ofBenjakul.
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August 2014

Genotoxicity and interference with cell cycle activities by an ethanolic extract from Thai Plumbago indica roots in human lymphocytes in vitro.

Asian Pac J Cancer Prev 2013 ;14(4):2487-90

Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.

In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR (12.5-100 μg/ml) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and 100 μg/ml were SCE levels significantly increased above that of the control (p<0.05) . EEPIR at a concentration of 500 μg/ml induced cell death as few mitotic cells were shown. Accordingly, EEPIR (25-100 μg/ml) is genotoxic in human lymphocytes and cytotoxic at concentrations of ≥ 500 μg/ml in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.
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http://dx.doi.org/10.7314/apjcp.2013.14.4.2487DOI Listing
October 2013

Using 6-gingerol content and gene mapping for identification of two types of ginger used in Thai traditional medicine.

J Med Assoc Thai 2012 Jan;95 Suppl 1:S135-41

Department of Applied Thai Traditional Medicine, Faculty of medicine, Thammasat University, Rungsit Campus, Klongluang, Pathumthani, Thailand.

Background: Two species of ginger were used in Thai traditional medicine as Zingiber officinale Roscoe and Zingiber ligulatum Roxb.

Objective: To investigate for identification two types of ginger by morphological and microscopic characters, DNA profiles, and determination of 6-gingerol content by HPLC.

Material And Method: Fresh rhizomes of two gingers, their ages more than one year were collected from 12 sources in 4 parts of Thailand. The fresh leaves were also collected for studying DNA profile by amplified fragment length polymorphism (AFLP) method.

Results: The morphological characters of two types of gingers were almost corresponded to AFLP patterns and they were identified as Z officinale Rocs. and Z. ligulatum Roxb. Microscopic examinations of dried rhizomes from the both species showed the same pattern. By means of HPLC and TLC methods, 6-gingerol content was found only in Z. officanale in range of 2.58-17.04% but disappeared in Z. ligulatum.

Conclusion: Determination of 6-gingerol content by HPLC or TLC pattern can be used to identified two types of ginger used in Thai Traditional Medicine.
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January 2012

In vitro cytotoxic activity of Benjakul herbal preparation and its active compounds against human lung, cervical and liver cancer cells.

J Med Assoc Thai 2012 Jan;95 Suppl 1:S127-34

Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.

Background: Benjakul [BEN], a Thai Traditional medicine preparation, is composed of five plants: Piper chaba fruit [PC], Piper sarmentosum root [PS], Piper interruptum stem [PI], Plumbago indica root [PL] and Zingiber officinale rhizome [ZO]. From selective interviews of folk doctors in Southern Thailand, it was found that Benjakul has been used for cancer patients.

Objective: To investigate cytotoxicity activity of Benjakul preparation [BEN] and its ingredients against three human cancer cell lines, large lung carcinoma cell line (COR-L23), cervical cancer cell line (Hela) liver cancer cell line (HepG2) as compared with normal lungfibroblast cell (MRC-5) by using SRB assay.

Material And Method: The extraction as imitated the method used by folk doctors was done by maceration in ethanol and boiling in water Bioassay guided isolation was used isolated cytotoxic compound.

Results: The ethanolic extracts of PL, ZO, PC, PS, BEN and PS showed specific activity against lung cancer cell (IC50 = 3.4, 7.9, 15.8, 18.4, 19.8 and 32.91 microg/ml) but all the water extracts had no cytotoxic activity. Three active ingredients [6-gingerol, plumbagin and piperine as 0.54, 4.18 and 7.48% w/w yield of crude extract respectively] were isolated from the ethanolic extract of BEN and they also showed cytotoxic activity with plumbagin showing the highest cytotoxic activity against COR-L23, HepG2, Hela and MRC-5 (IC50 = 2.55, 2.61, 4.16 and 11.54 microM respectively).

Conclusion: These data results may support the Thai traditional doctors who are using Benjakul to treat cancer patients and three of its constituents (6-gingerol, plumbagin and piperine) are suggested to be used as biomarkers for standardization of this preparation.
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January 2012

Determination of cytotoxic compounds of Thai traditional medicine called Benjakul using HPLC.

J Med Assoc Thai 2010 Dec;93 Suppl 7:S198-203

Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.

Benjakul is a Thai traditional medicine preparation, used for balanced health. From selective interviews of folk doctors in southern Thailand, it was used as the adaptogen drug for cancer patients. In our previous study, the ethanolic extract of Benjakul preparation exhibited high cytotoxic activity against lung cancer cell lines (COR-L23). Piperine has been identified as the main compound in the extract. In addition, plumbagin was found as the most cytotoxic compound. In this study, a reversed-phase high performance liquid chromatography (HPLC) method for quality control such as chemical fingerprint, quantification and stability of the ethanolic extract of Benjakul preparation was developed. The reversed-phase HPLC was performed with a gradient mobile phase composed of water and acetronitrile, and peaks were detected at 256 nm. Based on validation results, this analytical method is precise, accurate and stable for quantitative determination of piperine and plumbagin which are cytotoxic compounds isolated from the ethanolic extract of Benjakul preparation. This method could be suitable for analysis of Benjakul extract.
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December 2010