Safety Assessment of Schleichera oleosa Lour. Leaves Extract: Acute and Subchronic Studies.

<b>Background and Objective:</b> <i>Schleichera oleosa</i> (Sapindaceae) has been reported to be useful in traditional medicine and it has some potential pharmacological activities, such as anticancer, antioxidant and antimicrobial activities. This study aimed to assess its safety to provide complete data required for the development of <i>S. oleosa</i> as herbal medicine. <b>Materials and Methods:</b> The safety assessment of the extract was carried out by testing acute and subchronic toxicity in mice (male and female) and rats (male and female), respectively. The doses used in the acute toxicity test were 1000, 2000, 3000, 4000 and 5000 mg kg¹ of body weight and those in the subchronic treatment were 100, 200 and 400 mg kg¹ of body weight. <b>Results:</b> In the acute toxicity test, the <i>S. oleosa</i> leaf extract at all doses indicated that the LD₅₀ value of the extract was higher than 5000 mg kg¹ b.wt., which suggested that this extract is practically non-toxic according to the toxicity criteria. Furthermore, the subchronic toxicity test found that the administration of the extract to male and female rats at a daily dose of 100 and 200 mg kg¹ b.wt., for 90 days did not cause any significant change in blood haematology, blood biochemistry and histopathological picture of liver, kidney, heart, lymph and lung. Despite there being a significant increase in white blood counts, long-term use of the <i>S. oleosa</i> leaf extract is relatively safe. <b>Conclusion:</b> The results provided evidence regarding the potential of <i>S. oleosa</i> leaves to be used as herbal medicine. However, further research needs to be done to verify that activity and its safety in long-term use.

Patients' Perspectives of Interprofessional Collaboration in Breast Cancer Unit.

Interprofessional teamwork provides significant benefits for patients. However, qualitative research on interprofessional collaboration in the breast cancer unit is uncommon. Therefore, a qualitative study was conducted to assess the perceptions of outpatient breast cancer patients regarding interprofessional collaboration in the breast care unit of an Indonesian referral center hospital. The teamwork involved in the interprofessional collaboration included breast cancer specialists, pharmacists, and nurses. In this study, in-depth interviews were performed with nine breast cancer outpatients. All interviews were audio recorded, transcribed verbatim, and analyzed using thematic analysis. The findings were divided into two categories to gather breast cancer patients' viewpoints on interprofessional collaboration: (1) obstacle components to interprofessional collaboration: incompleteness of health personnel, no justification from health personnel, no knowledge of patients about health professionals, no involvement of patients in the therapy decision making; (2) enabling elements: patient-oriented, patient expectations, collaboration among healthcare personnel, patient participation in interprofessional collaboration, health personnel responsibilities, comprehensive hospital services. Respondents assumed interprofessional collaboration positively. However, several obstacles must be overcome to implement interprofessional collaboration in a breast care setting effectively. The research findings can be utilized to establish interprofessional collaborations aimed at improving quality healthcare in breast cancer units.

Caffeic Acid Phenethyl Ester as a DHODH Inhibitor and Its Synergistic Anticancer Properties in Combination with 5-Fluorouracil in a Breast Cancer Cell Line.

Introduction: A combination of chemotherapy agents is the best choice in breast cancer treatment to increase the patient survival rate. 5-fluorouracil (5-FU) is one of the drugs applied in combination with other drugs to control and delay development of cancer cells. Nevertheless, the occurrence of multidrug resistance and dose-limiting cytotoxicity have limited the efficacy of 5-FU treatment. Therefore, the discovery of new anti-breast cancer drugs should be pursued. Objective: To study potency of a promising naturally derived compound, caffeic acid phenethyl ester (CAPE), for breast cancer treatment in single and combination with 5-FU. Methods: Cytotoxicity of CAPE, 5-FU, and 5-FU+CAPE was studied by in vitro MTT experiment in MCF-7 cell line, and RT-PCR analysis was used to evaluate the change in gene expression due to the treatment. Moreover, an enzymatic assay and molecular docking analysis were applied to evaluate the possible mechanism of substance-induced apoptosis. Results: The study revealed that a single treatment of CAPE showed cytotoxicity with IC50 6.6 ± 1.0 µM and 6.5 ± 2.9 µM at 24 h and 48 h, respectively. Meanwhile, 5-FU showed cytostatic activity. The 5-FU + CAPE has a synergistic effect at 24 h treatment with a CI = 0.5 and an additive effect at 48 h treatment with CI = 1.0. CAPE was also found to enhances the mRNA expression of caspase-8 and BAX within 6 hours in combination with 5-FU compared to 5-FU treatment alone. Our study reveals a new mechanism of CAPE which is related to the inhibition of human dihydroorotate dehydrogenase (HsDHODH) with an IC50 of 120.7 ± 6.8 µM, by bound to the ubiquinone-binding site of the enzyme and could be responsible for inducing extrinsic and intrinsic apoptosis. Conclusion: This study demonstrated the cytotoxicity of CAPE potential to induce apoptosis of breast cancer MCF-7 cell line single and cytotoxic-cytostatic combination with 5-FU. Therefore, further studies to develop CAPE and its derivatives will be required to discover new candidates for breast cancer agents.

Cytotoxicity, Apoptosis, Migration Inhibition, and Autophagy-Induced by Crude Ricin from Ricinus communis Seeds in A549 Lung Cancer Cell Lines.

BACKGROUND Ricin protein derived from Ricinus communis seeds is known to have a high toxicity to humans and animals. Several studies revealed that ricin, belonging to ribosome inactivating protein-I, has cytotoxic properties against various types of cancer cell lines. MATERIAL AND METHODS Crude ricin (CR) from the seeds of R. communis was investigated for its cytotoxicity on the A549 cancer cell lines using the MTS assay, and the cell death mechanism was explored using flow cytometry and Western blot methods. The cell migration was measured using a scratch/wound-healing method and the autophagy activity was explored using Western blotting. RESULTS CR showed cytotoxicity against A549 cancer cell lines, with an IC50 of 40.94 ppm. CR induced apoptosis and necrosis, but apoptosis occurred more frequently than necrosis. Apoptosis induced by CR was mediated by the activation of caspase-9 and caspase-3. CR inhibited cell migration in a concentration- and time-dependent manner, with the highest effect occurred at the concentration of 1.0 ppm. The autophagic experiment showed that CR inhibited autophagy in A549 lung cancer cells by decreasing Beclin-1 levels while increasing Atg5 levels in a concentration-dependent manner and CR decreased LC3-II level while increasing p62 level. Cisplatin treatment also inhibited autophagy as it exhibited the same effect on those autophagic proteins as CR. CONCLUSIONS Our findings suggest that CR might be a potential candidate for anticancer drugs, but further study is needed to verify its anticancer properties.

Interprofessional collaboration in the breast cancer unit: how do healthcare workers see it?

BACKGROUND: Interprofessional collaboration has an important role in health care for breast cancer patients who are undergoing treatment at the hospital. Interprofessional collaboration has been reported to provide significant benefits for patients. However, qualitative research on interprofessional collaboration in the breast cancer department is rarely done, therefore, a study was conducted to determine the perception of health practitioners about interprofessional collaboration in the breast care unit at a referral centre hospital in West Java, Indonesia. METHODS: A qualitative study was carried out using in-depth interviews and focus group discussions (FGDs) with 15 healthcare personnel using total sampling. Participants were chosen among healthcare professionals who treat and in charge for outpatient breast cancer, but were not resident physicians. The FGD approach was used for nurses and pharmacists, and interviews were used for oncologists. The audio recordings of all interviews and FGDs were transcribed verbatim and evaluated using thematic analysis. RESULT: The findings were categorized into two categories to obtain health care workers' perspectives on interprofessional collaboration: (1) impediment factors: personality, lack of leadership, seniority, healthcare workers with double positions, the need for a clinical meeting, hospital bureaucracy, national health insurance implementation, issues with patients, hospital infrastructure, and evaluation and synchronisation; (2) existing supportive elements: effective cooperation, effective communication, clear job description, interpersonal relationships, Standard Operational Procedure (SOP) for cancer therapy, legality for inter-discipline cancer team, professional responsibility, integrated clinical pathway, patient centred care, and comprehensive health services. CONCLUSIONS: Interprofessional collaboration was seen positively by the respondents. However, there are several hurdles that must be overcome to apply interprofessional collaboration works effectively. The findings of this study can be used to build interprofessional collaborations targeted at enhancing quality health care in breast cancer units.

Structure elucidation of a new bicoumarin derivative from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm.

A new bicoumarin derivative, bidysoxyletine (1), was isolated from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm. The structure of 1 was elucidated by analysis of NMR, UV, IR, HR-ESITOFMS, and DDFT approach using the B3LYP exchange-correlation function for 13 C NMR and UV spectroscopic data. The results indicated that the structure of 1 possessed a dibenzonapthyrone skeleton.

Bidysoxyphenols A-C, dimeric sesquiterpene phenols from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm.

Three new sesquiterpene phenol dimers, bidysoxyphenols A-C (2-4), along with two known compounds, namely sesquiterpene phenol (1) and ionone derivatives (5), were isolated from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm. The structures of these new compounds, including their absolute configurations, were elucidated by nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, infrared spectroscopy, high-resolution electrospray ionization time-of-flight mass spectrometry, and electronic circular dichroism. Compounds 1 and 2 showed cytotoxicity against human promyelocytic leukemia cells, with IC50 values of 18.25 ± 1.52 and 39.04 ± 3.12 µM, respectively.

Phytochemical Screening, Toxicity Activity and Antioxidant Capacity of Ethanolic Extract of Etlingera alba Rhizome.

<b>Background and Objective:</b> <i>Etlingera alba </i>(Blume) A.D. Poulsen is one of the plants of the genus <i>Etlingera</i> which is commonly found in Southeast Sulawesi. The research is still lacking, thus, we assumed other species related to <i>E. alba,</i> specifically from the genus<i> Etlingera</i> that provides antioxidant and radical scavenging activity, namely <i>Etlingera elatior</i> (Jack) R.M. Smith. Thus, this study aimed to assess the antioxidant and toxicity activity as well as its secondary metabolites. <b>Materials and Methods:</b> <i>Etlingera alba</i> rhizome was extracted with 96% ethanol. The radical scavenging activity was assayed with 1,1-diphenyl-2-picrylhydrazyl (DPPH) and antioxidant activity was assayed with 2,2'-azino-bis-[3-ethylbenzothiazoline sulphonate (ABTS) assay for radical cation decolourization<i> in vitro</i>. Both Ascorbic Acid (AA) and Trolox were used as positive control. The secondary metabolites were identified by Thin Layer Chromatography (TLC) and LSMS/MS analyzed the difference between compounds. According to results performed with TLC and LCMS/MS. <b>Results:</b> The extract exhibited antioxidant properties using both DPPH and ABTS method. The LC₅₀ of the extract was 608.42±18.31 mg L¹.<i> Etlingera alba </i>rhizome extract contains alkaloids, flavonoids, terpenoids and steroids. The compounds detected in the extract were E-p-Coumaric acid aschantin, 2-Methoxyanofinic acid, Chavicol-ß-D-glucoside, Myristicanol B, ent-16α,17-Hydroxy-19-kaurenoic acid, 5-Hydroxy-7,8,2'-trimethoxyflavone, Methyl ursolate and Spinasterol. <b>Conclusion:</b> <i>Etlingera alba</i> rhizome contains several compounds that might be responsible for antioxidant activity and the extract itself classified as medium toxic.

Safety assessment of the Polypodium feei root extract: Acute and subchronic studies.

This study was performed to assess the safety of the oral acute and subchronic administration of Polypodium feei root extract through acute and subchronic studies in mice and rats, respectively. In the acute toxicity treatment, mice were grouped according to the dose (1000, 2000, 4000 and 5000 mg/kg, b.w) and were observed for mortality and toxicity signs for 14 days. In the subchronic treatment, there were six groups of rats (female and male), a control group, three test groups (100, 400, and 800 mg/kg, b.w), and two satellite groups (control satellite and satellite 800 mg/kg groups). The three test groups received the extract orally once daily for 90 days. No animals in the acute and subchronic treatment groups showed mortality and any signs of toxicity, with no significant difference in the body weight and organ index compared to the control. The LD50 of the extract was estimated to be higher than 5000 mg/kg, therefore regarded as practically non-toxic. The haematological profiles did not significantly change on exposure to the extract for 90 days, except the platelet count in the female animals which significantly decreased in animals treated with 400 and 800 mg/kg, returning to normal after 28 days of recovery. The 800 mg/kg dose significantly increased the urea concentration and induced lesions in the stomachs of female animals. However, this undesirable effect on the kidney was not strong, as the creatinine concentration remained in the normal limits, and the histopathological observations showed no alteration in the kidney tissues. No significant morphological alterations in organs were observed, only minor lesions in the liver. These results indicate that the P. feei root extract is safe for use as herbal medicine and recommended at doses lower than 400 mg/kg.

Cytotoxic and Antimigration Activity of Etlingera alba (A.D.) Poulsen Rhizome.

Etlingera alba is one of the Etlingera plants that might have anticancer activity. This study aims to investigate the cytotoxic and antimetastatic activity of E. alba rhizome fractions and migration cell assay against MDA-MB-231 cell lines, which are used for triple-negative breast cancer (TNBC) treatment assay. The cytotoxic activity was assayed using CCK-8 assay, while the antimetastatic was assayed using migration cell assay for the fractions A-F. They were followed by LCMS/MS profiling to determine the chemical contents in the most active fraction. According to results obtained, fraction B was the most active fraction for cytotoxic activity with an IC50 value of 65.43 µg/mL, while fraction E was the most active fraction for antimetastasis activity against migration rate doses of 50, 100, and 200 ppm which were 6.80, 3.66, and 3.00%, respectively. Several compounds in fraction B, such as rengyolone, licochalcone A, sugiol, and spinasterol, might have been known to have activity against cancer cells, as well as aschantin and lirioresinol B dimethyl ether from fraction E. In conclusion, the chemical components from E. alba rhizome fractions provided potency for discovering new agents for cancer treatment, specifically for TNBC.

In situ ophthalmic gel forming systems of poloxamer 407 and hydroxypropyl methyl cellulose mixtures for sustained ocular delivery of chloramphenicole: optimization study by factorial design.

BACKGROUND: Conventional drug delivery systems have some major drawbacks such as low bioavailability, short residence time and rapid precorneal drainage. An in situ gel drug delivery system provides several benefits, such as prolonged pharmacological duration of action, simpler production techniques, and low cost of manufacturing. This research aims to get the optimum formula of chloramphenicol in situ gel based on the physical evaluation. METHODS: The effects of independent variables (poloxamer 407 and hydroxypropyl methyl cellulose (HPMC) concentration) on various dependent variables (gelling capacity, pH and viscosity) were investigated by using 32 factorial design and organoleptic evaluation was done with descriptive analysis. RESULTS: The optimized formula of chloramphenicol in situ gel yielded 9 variations of poloxamer 407 and HPMC bases composition in % w/v as follows, F1 (5; 0.45), F2 (7.5; 0.45), F3 (10; 0.45), F4 (5; 0.725), F5 (7.5; 0.725), F6 (10; 0.725), F7 (5; 1), F8 (7.5; 1), F9 (10; 1). The results indicated that the organoleptic, pH, and gelling capacity parameters matched all formulas (F1-F9), however, the viscosity parameter only matched F3, F6, F8, and F9. Based on factorial design, F6 had the best formula with desirability value of 0.54, but the design recommended that formula with the composition bases of poloxamer 407 and HPMC at the ratio of 8.16 % w/v and 0.77 % w/v, respectively, was the optimum formula with a desirability value of 0.69. CONCLUSION: All formulas have met the Indonesian pharmacopoeia requirements based on the physical evaluation, especially formula 6 (F6), which was supported by the result of factorial design analysis.

Water-soluble propolis and bee pollen of Trigona spp. from South Sulawesi Indonesia induce apoptosis in the human breast cancer MCF-7 cell line.

Bee products are best known as one of the beneficial natural products providing multiple pharmacological effects, such as antimicrobial, antiviral, anti-inflammatory and anticancer effects. The present study aimed to identify potent products derived from the stingless bee Trigona spp. from Luwu Utara (South Sulawesi, Indonesia), focussing on the water-soluble extract of propolis and bee pollen, against the proliferation of the human breast cancer MCF-7 cell line. The results from DPPH (2,2-diphenyl-1-picrylhydrazyl) method of antioxidant assay revealed that water-soluble propolis and bee pollen had high antioxidant activity, with half-maximal effective concentrations against DPPH radicals of 1.3 and 0.4 mg/ml, respectively. Additionally, water-soluble propolis and bee pollen exhibited a significant antiproliferative activity in MCF-7 cells, with IC50 values of 10.8±0.06 and 18.6±0.03 mg/ml, respectively (P<0.05). Significant cytotoxic effects were observed after 24 h of treatment via microscopic and flow cytometric analysis, where a morphological change toward late apoptosis was observed. By contrast, honey had low antioxidant activity and no antiproliferative effect in MCF-7 cells. The water-soluble propolis also exerted its antiproliferative effect in the human keratinocyte HaCaT cell line. The antiproliferative activity was similar (P>0.05) at 24 and 48 h of treatment, with IC50 at 2.7±0.06 mg/ml and <0.4 mg/ml, respectively. Notably, bee pollen was less toxic to HaCaT cells after 24 h of treatment than the water-soluble propolis, with IC50>50 mg/ml. Its antiproliferative activity was significantly increased after 48 h of treatment, with IC50 at 9.6±0.07 mg/ml (P<0.05). In addition, similar to other poplar propolis, the high-performance liquid chromatography-ultraviolet and electrospray ionisation mass spectrometry analyses revealed that caffeic acid phenethyl ester was not the main bioactive compound of the samples examined. Furthermore, two major proteins (between ~50 and 75 kDa) were identified in the water-soluble propolis and bee pollen. The present results suggested that water-soluble propolis and bee pollen may have the potential to be elaborated further as a breast anticancer therapy.

Activity and Effectiveness of Recombinant hEGF Excreted by Escherichia coli BL21 on Wound Healing in Induced Diabetic Mice.

CONTEXT: Human epidermal growth factor (hEGF) has biological activities and can be used in medicines and cosmetics. A high level of effectiveness of hEGF can be obtained when three disulfide bonds fold perfectly. Extracellular secretion from E. coli BL21 using the PelB signal peptide is a new way to obtain hEGF with a structure that folds appropriately. OBJECT: This study aimed to determine the activity and effectiveness of recombinant hEGF excreted by E. coli BL21 on wound healing in induced diabetic mice. METHODS: Cell proliferation and migration tests were performed on NIH3T3 cells, followed by wound healing tests in induced diabetic mice, along with histological and endotoxin test at various hEGF concentrations (25, 50, and 75 µg/mL). RESULTS: Based on the results, hEGF at a level of 50 µg/mL showed optimal proliferation and migration activities. Wound healing in induced diabetic mice showed faster-wound closure within 12 days at hEGF 50 and 75 µg/mL with a percentage wound closure of 95% and 98.5%, respectively, which was significant versus control. In the histology test, the number of fibroblasts showed an increase and was significant at hEGF 75 µg/mL compared to the control group. The single test vial (STV) showed that hEGF solution was free of endotoxin. CONCLUSION: Recombinant hEGF produced by extracellular secretion using E. coli BL21 has optimal diabetic wound healing activity through increased fibroblast proliferation.

Antibacterial activity and subchronic toxicity of Cassia fistula L. barks in rats.

Increasing incidence of antibiotic resistance necessitates the development of more potent antibiotics. The aim of this work was to evaluate the antibacterial activity of Cassia fistula L. barks as an alternative agent for resistant pathogenic bacteria. The C. fistula barks were extracted with ethanol, followed by partition of the extract to give n-hexane, ethyl acetate and water fractions. An in vitro antibacterial assay was conducted to evaluate inhibitory activity of the extract and fractions against Salmonella typhosa and Shigella dysenteriae. An in vivo antibacterial activity was examined using S. typhosa-infected mouse models, in which the colony number of S. typhosa were counted from the infected rats' feces. Assesment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occured in biochemical parameters and hystopatological conditions of livers and kidneys. The results showed that the ethanol extract inhibited the growth of both S. typhosa and S. dysenteriae with the MIC of 0.3125% w/v, and the ethyl acetate fraction with the MIC of 0.625% b/v. In the in vivo antibacterial assay, the extract at three doses decreased the colony number of S. typhosa significantly, and after the fourth to sixth days, the precentage of decrease reached more than 90% by 1000 mg/kg dose. The subchronic toxicity test revealed that after the extract exposured for 90 days, a dose of 1000 mg/kg induced liver and kidney damages histologically, however, it returned to normal condition after 30 days of recovery. The results of this study indicated that the extract of C. fistula L. barks had potent in vivo antibacterial activity against S. typhosa as sample of resistant bacteria, and is safe to be used as a herbal medicine, preferably at a dose lower than 1000 mg/kg.

Apoptosis-mediated antiproliferation of A549 lung cancer cells mediated by Eugenia aquea leaf compound 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone and its molecular interaction with caspase receptor in molecular docking simulation.

In a previous study, 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (ChalcEA) isolated from the leaves of Eugenia aquea was reported to inhibit proliferation of the breast adenocarcinoma MCF7 cell line and to promote apoptosis via activation of poly(adenosine diphosphate-ribose) polymerase protein. The present study aimed to evaluate the inhibitory effect of ChalcEA on the proliferation of A549 lung cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and to examine the ability of ChalcEA to induce apoptosis through activation of the caspase cascade signaling pathway in a western blotting assay. The results revealed that ChalcEA inhibited proliferation of the A549 lung cancer cell lines in a time- and dose-dependent manner with IC50 values of 25.36 and 19.60 µM for 24 and 48 h treatments, respectively. Western blot analysis indicated that ChalcEA exerted its anti-proliferative effects by promoting apoptosis via the activation of caspase-9 and caspase-3. Based on in silico results, ChalcEA with the binding energy of -6.53 kcal/mol could compete better than 4-methyl benzenesulfonamide (-6.43 kcal/mol) as an inhibitor of caspase-3 (PDB: 2XYG). ChalcEA has potential since it has three hydrophobic features. These results provided a basis for further study of ChalcEA as an active compound for anticancer therapeutics.

Cytotoxicity Of Chalcone Of Eugenia aquea Burm F. Leaves Against T47D Breast Cancer Cell Lines And Its Prediction As An Estrogen Receptor Antagonist Based On Pharmacophore-Molecular Dynamics Simulation.

BACKGROUND: The 2',4'-dihydroxy-6-methoxy-3,5-3-dimethylchalcone (ChalcEA) isolated from Eugenia aquea Burm f. leaves has potential anticancer activity against human breast-adenocarcinoma cell lines (MCF-7) with an IC50 value of 250 µM. However, its apoptotic activity on the T47D breast cancer cell lines which is involving caspase-3 has not been investigated. MATERIALS AND METHODS: Therefore, this study aims to evaluate the cytotoxicity of ChalcEA on the T47D cell lines using the 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST) method and to predict its possible antagonistic activity on the human estrogen receptor alpha (hERα) using pharmacophore and molecular dynamics (MD) methods. The in vitro test of 10 synthesized ChalcEA derivatives was also performed as an insight into the further development of its structure as an anticancer agent. RESULTS: It is shown that ChalcEA has an IC50 of 142.58 ± 4.6 µM against the hERα-overexpressed T47D breast cancer cell lines, indicating its possible mechanism of anticancer activity as an antagonist of hERα. Pharmacophore study showed that ChalcEA shares similar features with the known hERα antagonist, 4-hydroxytamoxifen (4-OHT), which has hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), ring aromaticity (RA), and hydrophobicity (Hy) features. Molecular docking showed that ChalcEA formed hydrogen bonds with Glu353 and Arg394, and hydrophobic interactions in a similar manner with 4-OHT. Moreover, MD simulations showed that ChalcEA destabilized the conformation of His524, a remarkable behavior of a known hERa antagonist, including 4-OHT. Furthermore, the 10 best chalcone derivatives resulted from pharmacophore- and docking-based screening, were tested against the T47D cell lines. None of the derivatives have better activity than ChalcEA. It is suggested that the functional groups at the B-ring of ChalcEA are interesting to be further optimized in the next studies. CONCLUSION: ChalcEA might act as an antagonist toward hERα, thus warranting further investigation as a potential anticancer agent.

Antimalarial activity of extract and fractions of Castanopsis costata (Blume) A.DC.

OBJECTIVE: One of the biggest health problems in the world, which occurs in more than 90 countries, is the spread of malaria. Cep-cepan leaves (Castanopsis costata), was empirically used as an antimalarial herb in North Sumatra. Since its use has not been scientifically studied, we investigated the antimalarial activity of extract and fractions of C. costata against Plasmodium berghei ANKA (PbA) in a mouse model. MATERIALS AND METHODS: This experimental study was conducted using 32 male Balb/C mice. PbA inoculation was performed intraperitoneally with 106 parasites/mouse. Immediately after parasitemia reach >2% (day 0), the mice were treated orally with daily artesunate (36.4 mg/kg/day) (positive control), ethanolic extract (100, 200, and 400 mg/kg/day), and the fractions of water, ethyl acetate and n-hexane (108 mg/kg/day each) for 5 consecutive days (from day 0 to 4). Parasitemia inhibition was observed to determine the antimalarial activity of each type of C. costata extract and fractions. RESULTS: The administration of C. costata leaves ethanolic extract (100, 200, and 400 mg/kg) significantly inhibited the growth of PbA in Balb/C mice (42.66%, 66.2 1% and 80.99 % inhibition, respectively) (p<0.05). Similarly, all C. costata fractions also produced antimalarial activity against PbA with administration of the ethyl acetate fraction presenting the highest activity (79.85 % inhibition). CONCLUSION: The C. costata leaves showed antimalarial activity against P bA. However, further studies are necessary to elucidate the underlying mechanisms of this effect and the active compounds involved. Our current study revealed that C.costata could be a potential candidate to be used as a new antimalarial drug.

Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188.

OBJECTIVE: The aim of this study was to determine the best formulation of ophthalmic in situ gel preparation by two different bases, Poloxamer 188 and HPMC (hydroxypropyl methylcellulose), with physical evaluation, such as organoleptic, pH, viscosity, and gel capacity during 28 days of storage time. MATERIALS AND METHODS: The two different concentrations of the gel made by using Poloxamer 188 were F1 (5%) and F2 (10%), and those made by using HPMC were F3 (0.45%) and F4 (1%). RESULTS: The results of this study showed that formulation 1 (F1) was the optimum formulation, having pH 6.45, viscosity of 5.47 cP, and a better gel capacity than other formulas. CONCLUSION: In situ gel for ophthalmic preparations is developed to mask the limitation of conventional forms of ophthalmic preparation. In situ gel technology significantly increase the effectivity of drugs in the raw material and drug bioavailability in new drug delivery systems based on in situ gel concept.

Anticalculi Activity of Apigenin and Celery (Apium graveolens L.) Extract in Rats Induced by Ethylene Glycol-Ammonium Chloride.

OBJECTIVE: Kidney stones (nephrolithiasis) is one of the kidney diseases in the form of stones that contain crystal and organic matrix components. It is one of the most common diseases of the urinary tract. Calcium stone is the most important type of stone (80%) found in the case of kidney stones. Celery (Apium graveolens L.) is a plant rich in flavonoids, which can break down calcium crystals. Apigenin is considered to be one of the main flavonoids because of its presence and abundance in celery. This research aimed to compare the anticalculi effect of apigenin with that of celery extract. MATERIALS AND METHODS: Wistar albino rats were given ethylene glycol 0.75% (vol/vol) and ammonium chloride 2% (wt/vol) orally for 7 days in all groups to induce hyperoxaluria and Rats treated by Apigenin at doses 1.2, 2.4, and 4.8 mg/kg of rat body weight and celery extract at doses of 200, 400, and 600 mg/kg of rat body weight as anticalculi. Measurements of calcium levels in the kidneys and urine of rats was obtained using atomic absorption spectroscopy. Data obtained were statistically analyzed with the IBM SPSS by ANOVA Method version 21.0 probability value < 0.05 was considered significant. RESULT: The results showed that both apigenin and celery extracts caused kidney stone to decay. From the data Apigenin and celery showed that calcium level in urine there were significant differences (p value < 0.05) in treated group from negative control group but calcium level in kidney there were not significant differences (p value > 0.05). CONCLUSION: Celery extract has better ability to break down kidney stones than apigenin.

Inhibition of Phosphorylated c-Jun NH(2)-terminal Kinase by 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone Isolated from Eugenia aquea Burm f. Leaves in Jurkat T-cells.

BACKGROUND: Indonesian medicinal plants have been used for their anticancer activity for decades. However, the therapeutic effects of medicinal plants have not been fully examined scientifically. As cancer is a major health problem worldwide, searching for a new anticancer compound has attracted considerable attention. Our previous study found that 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone, an active compound isolated from leaves of Indonesian medicinal plants Eugenia aquea Burm f. (Myrtaceae), had anticancer activity in MCF-7 human breast cancer cells through induction of apoptosis. OBJECTIVE: To investigate the molecular mechanism of 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone antiproliferative activity. MATERIALS AND METHODS: Leaves of E. aquea were extracted by ethanol, fractionated by ethyl acetate, n-hexane, or water, and isolated for its active compound. Jurkat T-cells were treated with 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone for 12 and 24 h, and a cell viability assay and real-time-reverse transcriptase polymerase chain reaction for interleukin-2 (IL-2) mRNA measurement were performed. The effects of active compound to mitogen-activated protein kinases were also examined to investigate the mechanism of its antiproliferative activity. RESULTS: 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone inhibited Jurkat T-cell proliferation with a half maximal inhibitory concentration of 59.5 mM. Although IL-2 mRNA expression was slightly increased after treatment, it inhibited c-Jun N-terminal kinase expression but not p38 and extracellular signal-regulated kinase expression. CONCLUSIONS: Our study indicated that the molecular mechanism mediating the antiproliferative activity of 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone may be attributed to the stimulation of an immunological microenvironment in the cells. SUMMARY: 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone was isolated from Eugenia aquea. The antiproliferative activity of 2',4'-dihydroxy-6- methoxy-3,5-dimethylchalcone significantly showed in Jurkat T-cells with a half maximal inhibitory concentration of 59.5 mM through inhibition of c-Jun N-terminal kinase phosphorylation. Interleukin-2 mRNA expression was also slightly increased after treatment with the compound, and this result may be indicated to the stimulation of the immunological microenvironment in T-cells. Abbreviations used:E. aquea: Eugenia aquea, IL-2: Interleukin-2, MAPK: Mitogen-activated protein kinase, ERKs: Extracellular signal-regulated kinases, JNKs: c-Jun N-terminal kinases, p38: p38 MAPK, PI3K: Phosphatidylinositol-3 kinase, IC50: Half maximal inhibitory concentration.