@article {1958, title = {The effect of Sinensetin and Imperatorin on A-549 lung cancer cell viability in vitro}, journal = {Pharmacognosy Journal}, volume = {15}, year = {2023}, month = {March 2023}, pages = {38-46}, type = {Original Article }, chapter = {38}, abstract = {

Introduction: Lung cancer remains the leading cause of cancer death worldwide, so research is ongoing to discover new therapeutics, such as plant-derived bioactive compounds. For example, Sinensetin, a plant-derived polymethoxylated flavonoid, and Imperatorin, a natural furanocoumarin, have anti-cancer properties. This study assessed the effects of sinensetin and imperatorin separately and in combination on A-549 lung cancer cell viability. Method: The A-549 lung cancer cell line was treated with sinensetin (60 μM), imperatorin (30 M), or a combination of both compounds (Sin:Imp 30:30 μM; 50:50 μM and 60:30 μM) for 48 hours. Cell viability was then assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and apoptosis was determined using fluorescein isothiocyanate (FITC) Annexin-V/Propidium iodide staining. Results: The combination treatment of Sin:Imp 50:50 and Sin:Imp 60:30 μM reduced cell viability more than the individual treatment of sinensetin and imperatorin, with the lowest cell viability observed for the combination treatment of Sin:Imp 50:50 μM. Likewise, the combination treatment of Sin:Imp 50:50 μM induced the most apoptosis compared to individual treatment. Conclusion: Sinensetin and imperatorin can decrease A-549 lung cancer cell viability and are potent apoptotic inducers, especially when they are used in combination, therefore they are potential lung cancer therapeutics.

}, keywords = {A549, Apoptosis, Cell viability, Imperatorin, Sinensetin}, doi = {10.5530/pj.2023.15.6}, author = {Raden Anita Indriyanti and Eko Fuji Ariyanto and Hermin Aminah Usman and Ristaniah Rose Effendy and Diah Dhianawaty} } @article {2187, title = {Intravitreal Resveratrol as Anti Apoptotic Agent Against Retinal Ganglion Cell Loss in Ischemic Reperfusion Injury}, journal = {Pharmacognosy Journal}, volume = {15}, year = {2023}, month = {December 2023}, pages = {1207-1212}, type = {Research Article}, chapter = {1207}, abstract = {

Background: Glaucoma is an optic neuropathy caused by the apoptosis of retinal ganglion cells and results in progressive retinal ganglion cell injury. A decrease in intraocular pressure (IOP) is a modifiable risk factor for slowing the progression of the disease, and can be accomplished through medication, laser therapy, or surgery. Even though the intraocular pressure has decreased and attained normal levels, the injury to the retinal ganglion cells continues in some cases. It is believed that neuroprotective administration has a positive effect on preventing the loss of retinal ganglion cells. Methods: Bax and Caspase-3 expression were measured involving 20 eyeballs of Rattus Norvegicus by immunohistochemistry examination. I-R injury was developed by increasing intraocular pressure (IOP) through the intracameral balanced salt solution (BSS) injection, then lowered after 60 minutes. Samples were divided into 4 groups: control, no further injection group, phosphate-buffered saline (PBS)-injected group and resveratrol-injected group. Each group was enucleated at days 7, 0, 7, and 7, respectively. Data with a non-normal distribution were examined using the Kruskal-Wallis test, and if the outcome was significant, the Mann-Whitney test. Results: The highest mean Bax and Caspase-3 expression was found in PBS injected and enucleated at day 7 group (G2), 0.96{\textpm}0.40 and 0.72 {\textpm} 0.30, respectively. When compared to PBS injection, the expression of Bax and Caspase-3 was lower in the resveratrol-injected group. Conclusion: Bax and Caspase-3 expressions were lower in the intravitreal injection of Resveratrol in the dose of 100 {\textmu}M following the I-R injury group compared to the group without intravitreal Resveratrol injection.

}, keywords = {Apoptosis, Glaucoma, Ischemic-reperfusion injury, Neuroprotective, Resveratrol}, doi = {10.5530/pj.2023.15.219}, author = {Amelia Shinta Prasetya and Evelyn Komaratih and Wimbo Sasono and Mercia Chrysanti and Maria Debora Niken Larasati and I Ketut Sudiana} } @article {2089, title = {RETRACTED: The Effects of Andrographolide on Apoptosis in PC-3 Cell Line Via the Involvement of Caspases 3, 8 And 9}, journal = {Pharmacognosy Journal}, volume = {15}, year = {2023}, month = {August 2023}, pages = {612-621}, type = {Research Article}, chapter = {612}, abstract = {

The Article has been Retracted based on the Authors{\textquoteright} Request.

}, keywords = {Andrographolide, Anti-cancer, Apoptosis, Caspase., PC-3 cell line}, doi = {10.5530/pj.2023.15.128}, author = {Janany Manimaran and Daruliza Kernain Mohd Azman} } @article {1773, title = {An In Silico Study of Examining Bioactive Compounds from Azadirachta indica Juss. (Neem) as Potential Death Receptor 5 Inductor in Hepatoma Cells}, journal = {Pharmacognosy Journal}, volume = {14}, year = {2022}, month = {April 2022}, pages = {343-349}, type = {Research Article }, chapter = {343}, abstract = {

Hepatocellular carcinoma is a disease that occurs due to the uncontrolled growth of abnormal hepatocytes. While cancer cells will not die by itself, due to resistance to death receptors 5 (DR5)-mediated apoptosis. This study is aimed to investigate Azadirachta indica Juss. leaves compound, such as gedunin and nimbolide, in binding DR5 and stimulated the TNF-related apoptosis inducing ligand (TRAIL), native ligand binding to DR5, which has a role of pro-apoptotic by docking simulation. The ligand and protein preparations were done using Discovery Studio 2016 and Hex 8.0.0 for docking. Visualization was done using Discovery Studio 2016. The docking studies revealed that nimbolide has a lower binding energy with the DR5-TRAIL complex than gedunin. According to the findings, nimbolide is a more effective DR5-TRAIL binding inducer than gedunin and has a higher binding affinity for DR5-TRAIL. This interaction has the potential to significantly reduce DR5-TRAIL binding resistance. Nimbolide and gedunin can be considered as drugs that can sensitize TRAIL binding to DR5 and increase the activation of one of hepar cancers signaling apoptosis pathways.

}, keywords = {Apoptosis, Azadirachta indica Juss., Cancer, Death receptor 5, in silico}, doi = {10.5530/pj.2022.14.44}, author = {Ricadonna Raissa and Anna Safitri and Masruri Masruri and Ma Asuncion Guiang Beltran5 and Aulanni{\textquoteright}am Aulanni{\textquoteright}am} } @article {1420, title = {Both Ethanol and Ethyl Acetate Curcuma Zedoaraia Extract was Capable of Inducing Cells Death in T47D Cell Line Culture}, journal = {Pharmacognosy Journal}, volume = {13}, year = {2021}, month = {May 2021}, pages = {737-743}, type = {Research Article}, chapter = {737}, abstract = {

Introduction: Curcuma zedoaria (CZ) has been proven capable of inducing apoptosis in cells cancer. CZ extraction can be performed by ethanol and acetyl acetate as solvent. However, which one of these extracts is superior remains unclear. Objective: This study aimed to investigate the difference potential effect of ethanol and acetyl CZ extract on apoptosis of T47D cell line. Methods: In this study 21 wells were assign into seven groups: control group (T47D); treatment groups consisting of group of ethanol CZ extract 46 (EtZ-46); group of ethanol CZ extract 23 (EtZ-23); group of ethanol CZ extract 11 (EtZ-11); and group of ethyl acetate CZ extract 111 (AcZ-111); group of ethyl acetate CZ extract 55 (AcZ-55); and group of ethyl acetate CZ extract 27 (AcZ-27). In T47D group only loaded with T47D cell line; in treatment groups aside from loaded with T47D cell line culture, also treated with ethanol or acetyl acetate CZ extract respectively. Concentration of T47D cell was 5 x 104 T47D cells line in 100 μl suspension loaded on each well of 21 wells and kept in CO2 incubator overnight. The apoptosis cells were measured after 48 hours post CZ treatment. Results: Post Hoc analysis indicated that the number of apoptosis cells in AcZ-111 was significant higher compared to that of other groups, p\<0.05. Conclusion: Acetyl acetate CZ extract treatment with dose 111 μg was capable of inducing apoptosis in T47D cell line superior than that of other groups including ethanol CZ extract.

}, keywords = {Acetyl acetate, Apoptosis, Curcuma zedoaria, Ethanol, Necrosis, T47D cell line}, doi = {10.5530/pj.2021.13.94}, author = {Titiek Sumarawati and Chodidjah and Taufiqurrachman Nasihun} } @article {1674, title = {Cytotoxic Activity of Peronema canescens Jack Leaves on Human Cells: HT-29 and Primary Adenocarcinoma Colon Cancer}, journal = {Pharmacognosy Journal}, volume = {13}, year = {2021}, month = {November 2021}, pages = {1389-1396}, type = {Original Article}, chapter = {1389}, abstract = {

Background: In Indonesia, this species was well known in Sumatera, Kalimantan, Java, and Sulawesi. Peronema canescens Jack (Sungkai) was traditionally used as an anti-flatulent, fever, toothache. Sungkai leaves contain many secondary metabolites with potential anticancer activity. The reported anticancer research was still limited to the cytotoxic activity of chloroform extract on the HT-29 colon cancer cell line. However, it was necessary to uncover the underlying mechanism. Aim: The purpose of this study was to investigate the mechanism (such as cell cycle inhibition, induces cells apoptosis, and necrosis) of subfraction chloroform (SF3) from P. canescens extract has anticancer activity on HT-29 cells and primary Adenocarcinoma (AdenoCa pT3N1cM1) colon cancer cells. Materials and Methods: The extraction by maceration method using methanol solvent, the fractionation process was using vacuum column chromatography (VCC) with polarity gradient eluent. The cytotoxicity of SF3 was measured by MTT assay. The cell cycle inhibition, apoptosis induction, and necrosis cells were evaluated with the Flow cytometry method. Results: Cytotoxicity value (IC50) against AdenoCa cells was 1.897 μg/ml. The inhibition activity of synthesis and mitosis phase in cell cycle demonstrated that the different concentrations of SF3 have inhibition activity on HT-29 (29.614 μg/ml) of 26.79\% and 0.16\%, AdenoCa cells (14.807 μg/ml) of 10.27\% and 19.29\%, respectively. For induced apoptosis activity on HT-29 (29.614 μg/ml) and AdenoCa cells (14.807 μg/ml) were 26.58\% and 11.50\%, successively. Whereas, necrosis activity on HT-29 (29.614 μg/ ml) and AdenoCa cells (14.807 μg/ml) were 0.02\%, and 9.56\%, respectively. Conclusion: The subfractions chloroform (SF3) of P. canescens extract has potential activity on HT-29 and Adenocarcinoma cells through cell cycle inhibition, induces apoptosis and necrosis cells.

}, keywords = {Apoptosis, Cell cycle, Colon cancer cells, Necrosis, Peronema canescens Jack}, doi = {10.5530/pj.2021.13.176}, author = {Arsyik Ibrahim and Siswandono and Bambang Prajogo EW} } @article {1377, title = {Ergosterol Isolated from Agaricus blazei Murill N-Hexane Extracts as Potential Anticancer MCF-7 Activity}, journal = {Pharmacognosy Journal}, volume = {13}, year = {2021}, month = {March 2021}, pages = {418-426}, type = {Original Article}, chapter = {418}, abstract = {

Extracts and some of the Agaricus blazrei Murill isolates have potential anticancer. Ergosterol isolate from Amaouroderma rude can also inhibit the growth of MDA-MB-231 cancer cells through apoptotic pathways by increasing FOXO3 expression, while its potency against MCF-7 cells has not been reported. The purpose of this study was to isolate, determine the structure, determine the anticancer activity of MCF-7 cells, and the isolate mechanism by apoptosis from one of isolates the n-hexane A.blazei Murill extracts. This research method includes the isolation of compounds from A.blazei Murill extract by chromatography method guided using Bioactivity Guided Isolation. The structure elucidation of structure isolates used UV, NMR and MS spectroscopy. Anticancer activity test using the MTT cytotoxic test. Eludation of UV, NMR and MS structures showed a ergostrerol. The anticancer activity test showed IC50 values of 43.10 μg/ mL with the strong cytotoxic category. The mechanism of action is to increase apoptosis induction through inhibition of the cell cycle in the G2/ M phase. The conclusion of the isolated compound was ergosterol with an IC50 value of 43.10 μg / mL with an increased apoptosis induction mechanism through inhibition of the cell cycle in the G2/ M phase.

}, keywords = {Agaricus blazei, Apoptosis, Egosterol, MCF-7 cells, Murill extract}, doi = {10.5530/pj.2021.13.53}, author = {Misgiati Misgiati and Aty Widyawaruyanti and Sentot Joko Raharjo and Sukardiman Sukardiman} } @article {1375, title = {In vitro Cytotoxicity and Apoptosis-inducing Activity of Quercus infectoria Extracts in HeLa Cells}, journal = {Pharmacognosy Journal}, volume = {13}, year = {2021}, month = {March 2021}, pages = {401-410}, type = {Original Article}, chapter = {401}, abstract = {

Background: Quercus infectoria galls (QI) extracts were previously reported to have cytotoxicity effects towards human cervical cancer cells, HeLa. However, the underlying molecular mechanisms of the extracts have been poorly determined. Objective: The present study was undertaken to examine the effect of ethyl acetate extracts of QI (EAQI) on cell cytotoxicity and induction of apoptosis in HeLa cells. Materials and Method: The in vitro cytotoxicity was investigated by using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay and the OD values were read at 570 nm. Meanwhile the induction of apoptosis was measured by using acridine orange and propidium iodide (AO/PI) staining, flow cytometry analysis of annexin V/PI staining and cell cycle distribution. Results: MTT assay showed that EAQI exhibited cytotoxicity effect on HeLa cells with IC50 of 11.50 {\textpm} 0.50 μg/ml. HeLa cells underwent apoptosis in response to EAQI treatment, demonstrated by an increase in the percentage of apoptotic cell stained with AOPI from 1.00\% to 10.33\% compared to untreated cell population (p\<0.05) at 72 hours of treatment. The evidence of early apoptosis in treated cells were also observed in annexin V/PI staining. Furthermore, an increase of cell population in sub G0/G1 phase revealed that apoptosis as the mode of cell death in HeLa cells treated with EAQI. Conclusion: These findings indicated that EAQI significantly inhibits HeLa cell growth through induction of apoptosis. Further studies are needed to confirm the mechanism of cell death by expression of apoptotic cascade in HeLa cells treated with EAQI.

}, keywords = {Apoptosis, Cell cycle, Cytotoxicity, HeLa cells, Quercus infectoria}, doi = {10.5530/pj.2021.13.51}, author = {Illyana Ismail and Rapeah Suppian and Habsah Mohamad and Siti Aisha Mohd Radzi and Hasmah Abdullah} } @article {1409, title = {Isolation of Andrographolide from Andrographis lineata Wall. ex Nees var. lawii C.B. Clarke and its Anticancer Activity against Human Ovarian Teratocarcinoma}, journal = {Pharmacognosy Journal}, volume = {13}, year = {2021}, month = {May 2021}, pages = {660-668}, type = {Original Article}, chapter = {660}, abstract = {

Introduction: Andrographolide is a well-known anticancer phytochemical often isolated from Andrographis paniculata (Burm. f.) Nees. (Acanthaceae). Though Andrographis lineata Wall. ex Nees var. lawii C.B. Clarke (ALw) which also belongs to the same family has an adequate amount of andrographolide; remained untouched for isolation of andrographolide and anticancer studies. Therefore, this study was targeted to isolate the andrographolide from the leaves of ALw and to assess its role inthe induction of apoptosis against the human ovarian teratocarcinoma (PA-1) cell line. Methods: Column chromatography, thin-layer chromatography (TLC), preparative TLC were used for the isolation and purification while melting point, ultraviolet (UV)-visible spectroscopy, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), carbon-13 (C13) nuclear magnetic resonance (13C NMR) analysis were carried out for characterization of the compound. 3-(4,5-dimethylthiaxo-2yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay was carried out for cytotoxicity test and further Annexin-V staining, caspase 3 activity, B-cell lymphoma-2 (Bcl-2) activity, cell cycle analysis, and DNA damage study by terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assays were carried out for apoptosis study. Results: Andrographolide was isolated from the methanolic extract of leaves of ALw which had a melting point of 230 {\textordmasculine}C, λmax at 223 nm. FTIR results proved the presence of hydroxyl group, alkanes, carbon-carbon double bond, and a characteristic gamma lactone carbonyl. NMR data confirmed the 20 carbon structure. In the MTT assay cytotoxicity against PA-1 was at 3.7 μg/ml with other apoptotic assays supporting the induction of apoptosis by the compound at that concentration. Conclusion: ALw is proved to be an alternate source of andrographolide with potential abilities to induce apoptosis in ovarian cancer cells.

}, keywords = {Andrographis, Andrographolide, Anticancer activity, Apoptosis, Ovarian teratocarcinoma}, doi = {10.5530/pj.2021.13.84}, author = {Medha A. Bhat and Hosakatte Niranjana Murthy} } @article {1326, title = {Potential of Phaleria macrocarpa Leaves Ethanol Extract to Upregulate the Expression of Caspase-3 in Mouse Distal Colon after Dextran Sodium Sulphate Induction}, journal = {Pharmacognosy Journal}, volume = {13}, year = {2021}, month = {January 2021}, pages = {23-29}, type = {Original Article}, chapter = {23}, abstract = {

Ulcerative colitis (UC) is a part of incurable chronic inflammatory disease that has gained importance over the past few decades. A lot of research has been done to find effective treatments for UC, one of which is herbal medicine. Phaleria macrocarpa (PM), an Indonesian native plant, is thought to be an alternative therapy for UC because of its anti-inflammatory properties. Therefore, in this research, Phaleria macrocarpa Leaves Ethanol Extract (PMLEE) is used to assess its effect on UC by using Caspase-3 as apoptosis marker. PMLEE was made from dried material of PM that undergo maceration. Animals were separated into six groups: normal, negative control, positive control, and PMLEE groups (100, 200, 300 mg/kgBW). PMLEE was then injected to BALB/c mice that have been induced by dextran sodium sulphate (DSS) for 7 consecutive days. DSS is used to model UC in mice colon tissue. All animals were sacrificed and their colons were collected then stained with anti-Caspase-3. The stained sections were subsequently examined with ImageJ based on color intensity which generated H-Score as the results. Based on H-Score of each group, PMLEE 300mg has significantly upregulate the expression of Caspase-3 compare to the negative control (p=0.015). PMLEE also has a tendency to be dose dependent based on the significant difference between PMLEE doses. Therefore, it concludes that PMLEE is able to upregulate the expression of Caspase-3 in colon cells as in this study it was directly proportional. Key words: Mahkota Dewa, Inflammation, Apoptosis, Ulcerative colitis.

}, keywords = {Apoptosis, Inflammation, Mahkota Dewa, Ulcerative colitis}, doi = {10.5530/pj.2021.13.4}, author = {Kusmardi Kusmardi and Elvan Wiyarta and Ari Estuningtyas and Nurhuda Sahar and Yurnadi Hanafi Midoen and Aryo Tedjo} } @article {1642, title = {Single-Dose and Combined-Dose of Nanoparticles from Soursop Leaves (Annona muricata L.) and Sappan Wood (Caesalpinia sappan L.) Induced Apoptosis and Necrosis in HeLA Cells}, journal = {Pharmacognosy Journal}, volume = {13}, year = {2021}, month = {September 2021}, pages = {1134-1142}, type = {Original Article}, chapter = {1134}, abstract = {

Introduction: Apart from the medical advancement of chemotherapy, various plants were known as beneficial for cancer therapy because they can kill cancer cells selectively without damaging the normal cells. Here, we showed that nanoparticles formulated from chloroform fraction of soursop (Annona muricata L.) leaves and ethyl acetate fraction of sappan wood (Caesalpinia sappan L.) have anti-proliferative and cytotoxic effects on HeLa cervical cancer cells. Methods: The cytotoxic effect was evaluated using a single dose of each nanoparticle and a combined dose to obtain a synergistic effect. The mechanism of induced cell death via apoptosis or necrosis pathway was evaluated using flow cytometry by incorporating Annexin V and propidium iodide. Results: Synthesis of nanoparticles from the extract of soursop leaves (nano-SL) and extract of sappan wood (nano-SW) yielded particle sizes ranging from 248 to 317 nm. Nano-SL and nano-SW decreased the viability of HeLa cervical cancer cells in a dose-dependent manner with IC50 values of 63,32 μg/ml dan 40,88 μg/ml, respectively. The combined dose of 1/8 IC50 from both nanoparticles showed a strong synergistic effect, as shown by the combination index value of 0.13 based on the same mode of action and different modes of action. In HeLa cells treated with a combined dose of nanoparticles, the total apoptotic cells increased two times greater than that in control cells. Conclusion: Nano-SL and nano-SW induce apoptosis and necrosis in HeLa cells. Combined-dose of both nanoparticles produced a synergistic effect that could reduce the amount of the required individual dose while increasing the total effect.

}, keywords = {Annona muricata L., Apoptosis, Caesalpinia sappan L., HeLa cells, Nanoparticles, Necrosis}, doi = {10.5530/pj.2021.13.146}, author = {Okid Parama Astirin and Adi Prayitno and Anif Nur Artanti and Elisa Herawati and Afiyati Nur {\textquoteleft}Aini Saad and Ajeng Dara Firstlia} } @article {1256, title = {Black Horehound (Ballota nigra Linn) Induces Apoptosis in Prostate Cancer Cells (PC-3) Through Intrinsic Signalling Cascade}, journal = {Pharmacognosy Journal}, volume = {12}, year = {2020}, month = {September 2020}, pages = {1377-1382}, type = {Research Article}, chapter = {1377}, abstract = {

Background: Prostate cancer is the most commonly diagnosed cancer among men. The disease varies widely in its clinical aggressiveness. Ballota nigra Linn (Black horehound) is a three-foot, perennial herb of the family Lamiaceae and it has been shown to have various pharmacological properties such as antioxidant, hypoglycemic, neuro-sedative, antibacterial, insecticidal and anticholinesterase activities. However, the elucidation of B.nigra for its anticancer activity in prostate cancer has not been studied so far. Methodology: Prostate cancer PC3 cells were treated with different concentrations of B.nigra (50, 100, 200 \& 400μg/ml) for the analysis of Bcl-2, Phosphorylation of Bcl2 (p-Bcl2) and tumor suppressor protein p53, Case pase-3 and caspase-9 in PC3 cells. Results: The B.nigra ethanolic leaf extract reduced the levels of anti apoptotic proteins (Bcl-2, p-Bcl2) and increased the level of tumor suppressor protein p53, caspase-3 and 9 significantly (p\<0.05). Conclusion: Results of the study show that B.nigra has potential anticancer activity by modulating intrinsic activity of apoptotic signaling in PC-3 cells. Thus, B.nigra may have a potential therapeutic option for the treatment of prostate cancer.

}, keywords = {Apoptosis, Ballota nigra, Intrinsic pathway, PC3, Prostate cancer}, doi = {10.5530/pj.2020.12.190}, author = {Selvaraj Jayaraman and Ponnulakshmi Rajagopal and Vishnupriya Veeraraghavan and Poonguzhali Sivagnanam and Divya Ravikumar and Sumetha Suga Deiva Suga and Kavin Mozhi James and Surapaneni Krishna Mohan} } @article {1151, title = {Effect of Phaleria macrocapa on Atrophy and Apoptosis of Intestinal Mucous Cell and Phalerin Concentration at Portal Vein and Systemic Circulation in Adenocarcinoma Mice following Adriamycine and Cyclophosphamide Treatment}, journal = {Pharmacognosy Journal}, volume = {12}, year = {2020}, month = {May 2020}, pages = {603-610 }, type = {Research Article}, chapter = {603}, abstract = {

Introduction: Chemotherapy has been proven capable of reducing breast cancer cell progression; however the adverse effect also emerging. Thus, diminish those adverse effects with botanical product Phaleria macrocarpa (PM) as adjuvant therapy is necessary. Objective: This study aimed to evaluate the effect of PM treatment in combination with adriamycine and cyclophosphamide (AC) on intestinal apoptosis and their correlation with phalerin concentration in systemic circulation. Methods: In the experimental study, 30 female mice with adenocarcinoma were assign into 5 groups: Neg-G, only given aquadest; Portal vein group (PMV-G) and systemic circulation groups (PMC-G), were administered PM 0.146mg/day; Portal vein group (PMACV-G) and systemic circulation group (PMACC-G), were administered Phaleria macrocarpa 0,146 mg orally, Adriamycine 0,013 mg and Cyclophosphamide 0,0156 mg singgle dose intravenously. Phalerin concentration was measured by HPLC methods at minute 30, 60, 90, 120, 150, and 180 after treatment. At the end of study, intestinal mucous cell apoptosis was identified by TUNEL methods. Results: independent t test analyses showed that index of apoptosis of intestinal mucous cell were significant higher in PMAC-G compared to that of Neg-G and PM-G, p \< 0.05. In contrary, phalerin concentration in PMAC-G was significant lower compared to that of PM-G, p \< 0.05. The Pearson analysis indicated the inverse correlation (r= -736, p\>0.05) between apoptosis index with phalerin concentration. Conclusion: Treatment of PM in combination with AC has been proven able to increase intestinal mucous cell apoptosis and decrease phalerin concentration. However, the inverse correlation didnot exist.

}, keywords = {Apoptosis, Atrophy, Concentration, Phalerin}, doi = {10.5530/pj.2020.12.90 }, author = {Titik Sumarawati and Ignatius Riwanto and Soeharyo Hadisaputro and Edi Dharmana and Taufiqurachman Nasihun} } @article {1314, title = {Hepatoprotective Effect of Bioactive Fraction of Lagerstroemia speciosa (L.) Pers. Bark Against Monosodium Glutamate-Induced Liver Toxicity}, journal = {Pharmacognosy Journal}, volume = {12}, year = {2020}, month = {November 2020}, pages = {1630-1640}, type = {Research Article}, chapter = {1630}, abstract = {

Background: The phenolics and flavanoid enriched bioactive fraction of L. speciosa bark were reported for its medicinal value in various illness however hepatoprotective activity against monosodium glutamate-induced liver toxicity yet to be reported. Objective: To evaluate the hepatoprotective and antioxidant potential of L. speciosa bark extract fraction against monosodium glutamate-induced liver toxicity. Methods: The phytochemical constituent of ethyl acetate fraction of L. speciosa bark extract (LSE) were identified by GC-MS analysis. The antioxidant activity of LSE were analyzed with in-vitro antioxidant assay and subjected to evaluate hepatoprotective activity against monosodium glutamate induced liver toxicity in rat. Results: LSE evaluated as rich in phenolics and flavonoid content along with potent hepatoprotective activity. GC-MS analysis of bioactive fraction exhibits Palmitic Acid, Octadecanoic acid, 5-methyluridine, catechine, epigallocatechin, and norgestrel as major biologically active phytocompounds. Oral administration of LSE (100 and 200 mg/kg.) declined the elevated levels of the biochemical marker as well as interleukins while enhanced the enzymatic antioxidant activity and reduced the increased level of stress marker (MDA) in monosodium glutamate-induced rats. It also restored the altered expression level of proapoptotic genes, but there is no significant change in the expression level of the anti-apoptotic gene. LSE improved histopathology of the liver through the improvement of hepatocellular architecture, inflammation, and attenuation of vascular and cellular degeneration. Conclusion: The bioactive fraction of L. speciosa bark was found to exhibit strong antioxidant and hepatoprotection in monosodium glutamate induced liver toxicity in rats.

}, keywords = {Apoptosis, Lagerstroemia speciosa, Monosodium glutamate, Superoxide dismutase}, doi = {10.5530/pj.2020.12.223}, author = {Lal Chand Pal and Anil kumar and Veena Pande and Ch V Rao} } @article {1139, title = {Pimpinella Treatment on Reducing Apoptosis of Kidney Cells Following UVB Radiation in Rats}, journal = {Pharmacognosy Journal}, volume = {12}, year = {2020}, month = {May 2020}, pages = {503-509 }, type = {Original Article}, chapter = {503}, abstract = {

Introduction: Pimpinella alpina Molk (PM) is a botanical antioxidant was able to inhibit apoptosis in various cells. Apoptosis is a leading cause of tubular atrophy and therefore chronic kidney disease. However, the effect of PM on reducing apoptosis in kidney cells remains unclear. Objective: aim of this study to elucidate the effect of PM on reducing apoptosis in kidney cells. Methods: In the post test only control group design, 35 male rats were grouped into 7 comprise: NC-G, samples were neither exposure to UVB nor PM treatment; NG-7 and NG-15, all samples were only exposure to UVB irradiation for 7 days; P10-7, P15-7, P10-15, P15-15 groups, samples were exposure to UVB for 7 days and treated with PM for 7 and 15 days respectively. Bax and Caspase3 expression were assessed by rt-PCR and IHC staining method. Results: Statistical analysis showed that RNA-Bax and RNA-caspase3, Bax and caspase3 protein expression in P15-7, P10-15 and P15-15 were lower significantly compared to those of NG-7, p\<0.05, and no significant difference compared to those of NC-G, p \> 0.05. Conclusion: PM treatment with 100 and 150 mg/day for seven and fifteen days were able to decrease Bax and Caspase3 expression in kidney cells following UVB irradiation. Even, the decreased in Bax and caspase3 expression were comparable to normal.

}, keywords = {Apoptosis, Bax, Caspase3, Kidney Cells, Pimpinella alpina Molk}, doi = {10.5530/pj.2020.12.77 }, author = {Taufiqurrachman Nasihun and Eni Widayati} } @article {975, title = {Honokiol and Magnolol Induce Apoptosis and Cell Cycle Arrest in Human Ovarian Cancer Cells}, journal = {Pharmacognosy Journal}, volume = {11}, year = {2019}, month = {September 2019}, pages = {1114-1123}, type = {Research Article}, chapter = {1114}, abstract = {

Introduction: Ovarian cancer is a major cause of cancer-related death among women. The growth, persistence, and cancer metastasis are causes of poor prognosis and high mortality rate. Honokiol and magnolol are derivative compounds extracted from the root and stem bark of Magnolia officinalis. Many studies have reported that honokiol and magnolol have anti-tumour effects on various types of cancer. The present study investigates the anti-tumour effect of these compounds on human ovarian cancer. Methods: Ovarian cancer cell lines, SKOV3 and ES-2 cells were tested with honokiol and magnolol to determine their responses including the cytotoxicity, cell proliferation, induction of cell apoptosis and metastasis ability. Result: The results indicate that low concentrations of honokiol and magnolol suppressed the proliferation of ovarian cancer cells through induction of cell cycle arrest at G0/G1 and down-regulation of the cyclin D1 protein. These compounds also exhibited an anti-metastatic ability mediated by inhibiting migration, adhesion, and MMP activities. Additionally, high concentrations of honokiol and magnolol could activate cell death associated with the apoptosis signalling pathway, either along an intrinsic or extrinsic pathway. Conclusion: The data provides evidence that honokiol and magnolol have potential anti-tumour properties and minimal toxicity on normal cells, and could therefore be applied in the treatment of ovarian cancer.

}, keywords = {Apoptosis, Honokiol, Magnolol, Metastasis, Ovarian Cancer, Proliferation}, doi = {10.5530/pj.2019.11.174}, author = {Worawat Songjang and Arunya Jiraviriyakul} } @article {896, title = {Screening and Evaluation of Lectin and Anti-Cancer Activity from the Phloem Exudate/Sap of the Indian Dietary Ethnomedicinal Plants}, journal = {Pharmacognosy Journal}, volume = {11}, year = {2019}, month = {May 2019}, pages = {570-578}, type = {Original Article}, chapter = {570}, abstract = {

Objective: Lectins are extremely significant biomolecules to study several biological progressions. In this present investigation, we are screening the crude phloem exudate/ sap sample from different ethnomedicinal plants were evaluated for lectin and anticancer activity. Methods: The lectin activity of crude phloem exudate/sap samples were confirmed by haemgglutination assay and anticancer activity by using trypan blue, MTT and in-ovo CAM angiogenic assay. The tumor cell nuclei resulting in Giemsa stain, AO/EtBr stain, DNA Fragmentation and Caspase- 3 inhibitor assay. Results: Our experimental data show that the phloem exudate/sap sample S2 (Musa Acuminata), sample S4 (Euphorbia Geniculate) exerting the potent lectin activity, sample S5 exerting very low lectin activity against the trypsinized rabbit erythrocytes and decreases the cell viability in EAC cells in-vitro. Sample S2, S4 and S5 exerts significant cytotoxic effect against the various human cancer cell lines and regressed the neovasculature (development of new blood vessels) in the developing CAM embryos when compared to the other crude samples. The apoptotic inducing activity of crude phloem exudate/sap samples was revealed by DNA fragmentation assay, caspase-3 inhibitor assay and cellular morphology were studied by fluorescence staining methods. Conclusion: This study reports that some of the isolated crude phloem exudate/sap samples show potent lectin activity and anti-cancer activity in different human cancer cell lines. The further additional experiment needs to purify and characterize the bioactive lectin components from the potent sample which is responsible for pro-apoptotic, anti-angiogenic activity and mechanism involved.

}, keywords = {Angiogenesis, Apoptosis, EAC, Haemagglutination, Lectin, VEGF}, doi = {10.5530/pj.2019.11.91}, author = {Balaji Kyathegowdanadoddi Srinivas and Madhu Chakkere Shivamadhu and Preethi Saligrama Devegowda and Gurukar Mathew and Theethagounder Tamizhmani and Senthilkumar Gnanavadevel Prabhakaran and Shankar Jayarama} } @article {531, title = {Andrographolide Induced Apoptosis in NALM-6 Cells Mediated Through the Cell Cycle Arrest and Nuclear Fragmentation}, journal = {Pharmacog Journal}, volume = {10}, year = {2018}, month = {January-2018}, pages = {210-214}, type = {Original Article}, chapter = {210 }, abstract = {

Introduction: Andrographis paniculata is an herb widely cultivated in South and Southeastern Asia. It has been traditionally used to treat infections and other Physiological disorders for several hundreds. We investigated the anti-leukemic potential of Andrographolide (AGP) isolated from the leaves of this plant against an array of cancer cells to investigate its most efficacies in a particular cancer type. Methods: AGP was isolated from Andrographis paniculata leaves by using column chromatography. The structure was further determined by LC-MS, 1H NMR and 13C NMR. AGP was initially tested against four different cancer cell lines, namely NALM-6 (pre B-ALL), K562 (CML), A549 (lung carcinoma) and MCF-7 (breast carcinoma) using MTT assay at different time points and different concentrations. The effect of the isolated biomolecule was also investigated in inducing apoptosis through the study of cell cycle progression using flow cytometry by PI staining and nuclear fragmentation pattern by DAPI staining and fluorescence microscopy. Results: the spectral analysis of the isolated bio-molecule assured that the compound was AGP. MTT assay data indicated that AGP was most potent to induce cytotoxicity in NALM-6 cells. Further investigation revealed that it effectively induced apoptosis by arresting cell cycle progression and increased the nuclear break down in NALM- 6 leukemic cells. Conclusion: Our study efficiently demonstrated that the AGP isolated from Andrographis paniculata induced apoptosis in NALM-6 cells, which could be used in the therapeutic intervention of leukemia in the future.

}, keywords = {Andrographis paniculata, Andrographolide, Apoptosis, Cell cycle, Cytotoxicity, Leukemia}, doi = {10.5530/pj.2018.2.36}, url = {http://fulltxt.org/article/466}, author = {Swadesh Sarkar and Priya K Gopal and Santanu Paul} } @article {569, title = {Anti-Proliferative Properties of Terminalia sericea Burch. Ex Dc Leaf Extracts Against Caco2 and HeLa Cancer Cell Lines}, journal = {Pharmacognosy Journal}, volume = {10}, year = {2018}, month = {March 2018}, pages = {408-415}, type = {Original Article}, chapter = {408}, abstract = {

Introduction: Terminalia spp. are characterised by their high levels of antioxidant phytochemicals and several species have anticancer activity. This study examines the anti-proliferative activity of T. sericea leaf extracts against Caco2 and HeLa carcinoma cell proliferation. Methods: Solvent extracts were prepared from T. sericea leaves and their antioxidant capacities were determined by the DPPH free radical scavenging assay. Anti-proliferative activities against Caco2 and HeLa cancer cells were determined by an MTS based cell proliferation assay. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: The methanolic and aqueous T. sericea leaf extracts displayed high antioxidant capacities (equivalent to 150 and 340 mg of ascorbic acid per gram of plant material extracted respectively). In contrast, the ethyl acetate, chloroform and hexane extracts had relatively low antioxidant contents (\≤5 mg of ascorbic acid equivalents per gram of plant material extracted). The antioxidant contents of the T. sericea leaf extracts correlated with the ability of the extracts to inhibit proliferation of Caco2 and HeLa cancer cell lines. The high antioxidant methanolic and aqueous extracts were potent inhibitors of cell proliferation, with IC50 values 120-1400 \μg/mL. The aqueous T. sericea leaf extract was particularly effective, with IC50 values of 528 and 120 \μg/mL against Caco2 and HeLa cells respectively. The methanolic extract also displayed good, albeit substantially less potent, antiproliferative activity against HeLa cells, with an IC50 of 1358 \μg/mL. In contrast, the lower antioxidant content extracts generally did not inhibit cancer cell proliferation. Cell imaging studies detected morphological features consistent with apoptosis in Caco2 cells exposed to sub-lethal concentrations of the methanolic and aqueous T. sericea leaf extracts, indicating that these extracts are functioning by cytotoxic mechanisms. The aqueous T. sericea leaf extract displayed low to moderate toxicity in the Artemia franciscana bioassay, with an LC50 value of 737 \μg/mL. All other extracts were nontoxic. Conclusion: The antiproliferative activity and low toxicity of the T. sericea methanolic and aqueous leaf extracts extracts against HeLa and Caco2 cancer cell lines indicates their potential in the treatment and prevention of some cancers.

}, keywords = {Anticancer activity, Antioxidant Capacity, Antiproliferative Activity, Apoptosis, Combretaceae, DPPH, Silver Cluster Leaf}, doi = {10.5530/pj.2018.3.67}, url = {http://fulltxt.org/article/499}, author = {BiYun Gu and Joseph Shalom and Ian E. Cock} } @article {598, title = {Purified Anthocyanin from in vitro Culture of Bridelia retusa (L.) Spreng. Capable of Inhibiting the Growth of Human Oral Squamous Cell Carcinoma Cells}, journal = {Pharmacognosy Journal}, volume = {10}, year = {2018}, month = {March 2018}, pages = {559-566}, type = {Original Article}, chapter = {559}, abstract = {

The present study aims in vitro cell suspension culture of Bridelia retusa, isolation of anthocyanin, purification, fractionation and its anti-metastatic potential against oral squamous carcinoma cells. Experimental results reveal that 2, 4-D either alone or in combination with kinetin supplemented in MS medium showed significant initiation of callus from leaf explants than stem. Growth hormones, pH, light, and carbon source influence anthocyanin synthesis. Maximum callus induction was noticed with 2.5 mg/L N6-benzyladenine (BA) + 2 mg/L 2, 4-dichlorophenoxyacetic acid (2, 4-D) (98.9\%). Fresh and dry weight of the calli were i.e., 1.9 \± 0.04 and 0.45 \± 0. 03 g respectively. Optimal response was seen with light on MS medium contain 4\% glucose + 2.5 mg/L BA and 2 mg/L 2, 4-D at pH 3.5 yielded 2.8 mg /g of anthocyanins. Suspension culture medium fortified with 2, 4-D (2.5 mg/L) + BA (2 mg/L) at pH 5.0 induced anthocyanin production at pH 4.4 \– 4.6. HCl-ethanol extraction for 90 min yielded the maximum anthocyanin content. Fractionation of anthocyanin using HPLC coupled with mass spectrometry revealed 07 fractions such as acylated cyanidins, two peonidins, cyanidin 3-p-coumaroyl and feruloyl diglucoside-5-glucosides. In the search of novel therapeutic drugs against cancer, cytotoxicity effect of B.retusa anthocyanin extracts on human oral squamous cell carcinoma (SCC4, SCC9 and SCC25) cells using cell adhesion and cell viability assay was carried. The morphological alterations in SCCs cells after treatment with B.retusa anthocyanin includes nuclear condensation, fragmentation and apoptotic cells as revealed by Hoechst stain. Flow cytometry showed arresting of SCC25 cells mostly in the G0/G1 and S-G2/M stages with a concomitant up regulation of sub-G1 fraction, indicating cell death by apoptosis. Apoptosis was further substantiated by the activation of caspase-3 expression in the SCC25 cells treated with B.retusa anthocyanin. Thus, it is possible to suggest that B.retusa anthocyanin cause apoptosis of SCCs and warrant further investigation using animal models.

}, keywords = {Anthocyanin, Anti-metastatic potential, Apoptosis, Bridelia retusa, Cell suspension, in vitro culture, Purification}, doi = {10.5530/pj.2018.3.91}, url = {http://fulltxt.org/article/524}, author = {Aswathy Jayasree Madanakumar and Bosco Lawarence and Manoj GS and Murugan Kumaraswamy} } @article {416, title = {Triptolide Mediated Amelioration of Breast Cancer via Modulation of Molecular Pathways}, journal = {Pharmacognosy Journal}, volume = {9}, year = {2017}, month = {September 2017}, pages = {838-845}, type = {Original Article}, chapter = {838}, abstract = {

Triptolide is the main bioactive molecule isolated from a root extract of Tripterigium wilfordii Hook F. of Celastraceae family. Chemically, it is a diterpenoid triepoxide molecule and its chemical formula is C20H24O6. Its five-membered unsaturated lactone ring (D-ring) is crucial for anti-tumor potential and carbonyl group at C-18 position is essential to exert important influence on the interaction between triptolide and the targeted protein(s). It is bio-synthesized from deoxy-D-xylullose-5-phosphate (DOXP) pathway in the cell. Triptolide can induce apoptosis in a number of breast cancer cells by up-regulating different pro-apoptotic and down-regulating different anti-apoptotic molecules. In vitro experiments indicate that it can down regulate several cell cycle related genes and induces S-phase cell cycle arrest. Triptolide treatment can also modulate the expression of different cell signaling molecules, e.g. ERK, NF-\κB, FAK, VEGF, \β-catenin, AKT etc. In vivo experiments indicate that triptolide can effectively reduce breast tumor growth in the mouse model. Apart from the single drug treatment, triptolide can effectively be applied in combination therapy. Application of Triptolide with other chemotherapeutic drugs, very efficiently check the proliferation of tumor cells which reduces the effective concentration of the commercially available drugs thus reducing their toxic sideeffects. Although triptolide is very effective against a number of diseases, its higher degree of multi-organ toxicity limits its use of further clinical trial. Therefore, to reduce the toxic effects, a number of strategies have been developed which increase its water solubility and at the same time decrease the toxic effect. In this review article, we have addressed how triptolide participates in the antitumor processes in breast cancer cells.

}, keywords = {Apoptosis, Breast cancer, Cytotoxicity, Molecular pathway., Tripterigium wilfordii, Triptolide}, doi = {10.5530/pj.2017.6.131}, url = {http://fulltxt.org/article/184}, author = {Swadesh Sarkar and Santanu Paul} }