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Objective Nature has provided us with many pharmaceutical resources so far. Breast cancer shows an increasing trend in the world for the last decade and becomes one of five leading causes of death. Among the plants, Melia azedarach L. has been used widely in traditional medicine for many ailments including breast cancer. Following our previous findings that the ethyl acetate fraction was the most active cytotoxic fraction against T47D cells, we aimed to isolate the cytotoxic compounds and further elucidate their apoptotic mechanisms. Methods The compounds were isolated through a series of chromatography with cytotoxicity evaluations. Identification of the isolated compounds was achieved by intensive spectroscopic analysis such as NMR, MS, and IR spectra. Cytotoxicity was evaluated by MTT method using doxorubicin as a reference compound. The expression of apoptosis-related factors was quantified by flow cytometry and immunocytochemistry. Results Two isomers of pregnane steroids with molecular weight 330.2087 (C21H30O3) were isolated from the EtOAc extract. Spectroscopic analysis revealed the structures as 17-ethylene-3,4-dihydroxy-14-methyl-18-norandrostene-16-one (1) and 17-ethylene-3,4-dihydroxy-5-pregnene-16-one (2), respectively. These compounds showed moderate cytotoxicity (IC50 172.9 and 62.2 µg/mL, respectively) comparable to doxorubicin (IC50 3.08 µg/mL). The execution of apoptosis may be related to the increase of the ratio of BAX/bcl-2 of the cells. Conclusion: The EtOAc fraction of Melia azedarach L. leaves and the isolated 5-pregnene-16-one steroids are promising reagents for breast cancer treatment by introducing apoptosis to tumor cells. However, further researches are required to highlight its safety and usage in vivo. .

The coronavirus disease 2019 (COVID-19) pandemic has attracted worldwide attention. Andrographis paniculata (Burm. f) Ness (AP) is naturally used to treat various diseases, including infectious diseases. Its Andrographolide has been clinically observed for anti-HIV and has also in silico tested for COVID-19 main protease inhibitors. Meanwhile, the AP phytochemicals content also provides insight into the molecular structures diversity for the bioactive discovery. This study aims to find COVID-19 main protease inhibitor from AP by the molecular docking method and determine the toxicity profile of the compounds. The results obtained two compounds consisting of flavonoid glycosides 5,4'-dihydroxy-7-O-β -D-pyran-glycuronate butyl ester and andrographolide glycoside 3-O-β-D-glucopyranosyl-andrographolide have lower free binding energy and highest similarity in types of interaction with amino acid residues compared to its co-crystal ligands (6LU7) and Indinavir or Remdesivir. The toxicity prediction of the compounds also reveals their safety. These results confirm the probability of using AP phytochemical compounds as COVID-19 main protease inhibitors, although further research must be carried out.

Background Natural resources provide more efficient and safer alternatives in managing diabetes compare to the synthetic oral anti diabetes (OAD). The plants not only have hypoglycemic effect, but also prevent its complications; in which no synthetic drugs provide of both properties. Among antidiabetes plants, mahogany seed (Swietenia macrophylla) has been used as traditional medicine in Indonesia and India, though most popular utilized as timber wood. Methods The present study was performed of chemotaxonomic approach to review its phytochemical and anti-diabetic properties of Swietenia mahagoni (L.) Jacq seed/bark/leaves. The qualitative systematic review (SR) was carried out by analysing indexed journals and peer reviewed of Swietenia and Swietenia spp from Scopus, PubMed, Medline, Google Scholar, and Research Gate. Data selection criteria are accordance to botany, phytochemistry, in vitro, in vivo, and clinical test of related subject. The keywords used for the search in the databases were Swietenia, Swietenia mahagony, diabetes, and diabetes plants. Results Swietenia mahagoni (L.) Jacq. extracts have shown in vitro, in vivo and limited clinically test of its anti-diabetic properties. Ethanolic/methanolic/aqueous/petroleum/n-hexane extracts of mahagonis's seed/bark or leaves have anti-diabetic activities comparable to the synthetic drug and observed no to relatively mild toxic effect. The hypoglycemic mechanism suggested via reducing blood glucose level, restoring liver and β-cells islet function (might) blocking epinephrine function, inhibiting of α-amylase and β-glucosidase, antioxidant and antihiperlipidemia. Phytochemical compounds of S. mahagoni consist of the phenolics (flavonoids (swietemacrophyllanin, catechins and epichatechins) and tannins), triterpenoids and tetranortriterpenoids (limonoids: mahonin, secomahoganin, swietmanins, swiemahogins, swietenine and swietenolide), saponins and alkaloids which are known as anti-diabetic bioactive principles. Conclusion S. mahagoni was potentially used and developed as an antidiabetes source. To use it as an antidiabetic further, more extensive clinical trials and biomarkers of active compounds determination are needed., Toxicology; Diabetes; Hypoglycemic; Mahogany; Meliaceae; Swietenia sp

Graphical abstract, Highlights • 1st report on physical qualities and phytochemical content of M. azedarach wild type leaves extract and fractions. • Ethyl acetate fraction was the most active against bio-selective hormonal breast cancer T47D cell cytotoxic and antioxidant activities. • The phytochemicals content of active fraction was steroids and triterpene saponin, limonoid (toosendanin, meliarachin, salannin, salannal, 12-hydroxyamoorastatin, meliacarpinin and its derivates), and flavonoids (quercetin glycoside). • Significant (p, Melia azedarach L. is used widely in traditional medicine for local or systemic ailments. Although studies exist on phytochemicals and potencies of Chinese and Indian cultivars of Melia, the present study investigated in vitro antioxidant properties of Melia wild type and its cytotoxicity against T47D cell. The ethanolic extract of the Melia leaves was fractionated with n-hexane, ethyl acetate and water, and the secondary metabolites were obtained. The antioxidant properties were determined with IC50 DPPH (2,2-diphenyl-1-pycrylhydrazyl) radical and FRAP (ferric reducing antioxidant power), while the cytotoxicity was determined with the MTT method. The total phenolic (TPC) and β-sitosterol (SC) contents were also measured. The results showed that the ethyl acetate fraction had higher antioxidant and cytotoxic activities (IC50 211.89 ± 10.86 and 147.90 ± 8.49 μg/mL, respectively) than others. Significant (p

Three new flavonoid glycosides named isolinariins C, D and E (1-3), two known flavonoid glycosides (4, 5) and three known flavonoids (6-8) were isolated from the whole plant of Linaria japonica. The structures of these compounds were determined mainly by spectroscopic analyses. The bioactivities of these isolated compounds were evaluated for their inhibitory activities against human cell line A549, collagenase, and advanced glycation end product (AGE) formation. Among the isolated compounds, isolinariins C, D and E (1, 2 and 3) showed inhibition toward AGE formation (IC50 values of 34.8, 35.0 and 19.5 µM, respectively). And linariin (4), pectolinarin (5) and luteolin (8) were found to be active against collagenase with IC50 values of 79.4, 78.6 and 40.5 µM, respectively, without significant cytotoxicity at these concentrations.

Five new cis-ent-clerodanes, linarenones A–E (1–5) and two known compounds (6 and 7) were isolated from whole plant of Linaria japonica. The structures of these compounds were determined by various spectroscopic analyses (UV, IR, HR–ESI–MS, 1D and 2D NMR). The absolute configuration of five new diterpenoids was confirmed by circular dichroism (CD) analysis and chemical conversion. Cytotoxicity of the isolated compounds against A549 cell lines and Leishmania major were evaluated. The new cis-ent-clerodane 3 was found to be moderately active against A549 cell lines, and new cis-ent-clerodanes 1, 6 and desacetyl-linarienone (7) were active against L. major.

Background: a Migraine is a headache with pain attacks lasting 4 - 72 hours. Pain is usually unilateral, it is pulsating, the intensity of pain is moderate to severe and aggravated by activity, and can be accompanied by nausea, vomiting, photophobia, and phonophobia. Headaches are one of the most common disorders of the nervous system. It has been estimated that 47% of the adult population experience headaches at least once in the past year in general. According to TCM, headache is a disease with a headache accompanied by a variety of symptoms, where the cause is an external pathogen and causes in the body. Acupressure is one form of traditional treatment skills by suppressing acupuncture points with emphasis on using fingers or blunt objects on the surface of the body, in order to support promotive, effective, rehabilitative efforts. In addition to acupressure, herbal drinks can also be used to reduce pain, namely aromatic ginger. Purpose: Knowing the effect of acupressure and aromatic ginger herbs (Kaempferia galangal Linn.) combination therapy in reducing migraine complaints. Methods: Acupressure at Fengchi point (GB20) 50 times, Taiyang (EX-HN5) 50 times, Sanyinjiao (SP6) 30 times, Taichong (LR3) 50 times and aromatic ginger herbs (Kaempferia galangal Linn.) 15 grams for 28 days. Results: Migraine complaints decreased from 5 times a month to 3 times a month. No more complaints of nausea, hypochondrium pain, diarrhea, and insomnia. Conclusion: Acupressure at Fengchi point (GB20) was 50 times of the pressure, Taiyang (EX-HN5) was 50 times of the pressure, Sanyinjiao (SP6) was 30 times of the pressure, Taichong (LR3) was 50 times of the pressure and the aromatic ginger herbs (Kaempferia galangal Linn.) As much as 15 grams for 28 days could reduce migraine complaints.

Aaptos suberitoides marine sponge produce many kinds of secondary metabolites. The purpose of this study were to examine the cytotoxic, proliferation inhibition and apoptosis induction of marine sponge A.suberitoides. The sponge was extracted with 96 % ethanol. Ethanol extract cytotoxicity assay were performed with MTT method (Microculture Tetrazolium) against to cell line of T47D. The proliferation inhibition were done by doubling time. The apoptosis induction by observing the treated cell morphology after staining with acrydine orange. The results show that cytotoxic activity of the ethanol extract was 153.109 µg/mL, inhibits cell proliferation cell lines of T47D at 24 hours of incubation and apoptosis induction.

It has been well documented that chemical carcinogen, 7.12 dimethylbenz(a)anthracene (DMBA), plays a role in the incidence and growth of mammary cancer. Present study was designed to investigate the influence of Andrographis paniculata extract on telomerase activities on DMBA induced breast cancer in the female rat Sprague Dawley strain. DMBA-induced mammary cancer is a useful model to investigate the changes of epithelial cells that occur during mammary cancer progression. Mammary cancer model was induced 10 times twice a week by oral DMBA 20 mg/kg body weight. Mammary cancer occurred in 75 % animals nine weeks after oral administration of DMBA, it was represented with nodule on the mammary gland and the increasing of mammary gland volume compare with normal control F(1.8) = 731.711; p < 0.001. This study was also designed to investigate the effect of Andrographis paniculata extract mammary carcinoma induced by DMBA. Administration of three different dose of Andrographis paniculata (100 mg/kg, 300 mg/kg and 1000 mg/kg) had statistically different with mammary gland volume of DMBA treated rat F (4.17) = 92.777; p

Calotropis gigantea (L.) W. Aiton (C. gigantea) is a medicinal plant that has been empirically proven to have anticancer activity. In a previous study, it showed that the fraction of ethyl acetate from the root part of C. gigantea had higher anticancer activity than the other fractions. It suspected that the ethyl acetate fraction of C. gigantea root contained active compounds that has anticancer properties. This study aimed to determine the anticancer activity of active compounds from the ethyl acetate fraction of C. gigantea root regarding induction of apoptosis, cell cycle arrest, and expression of caspase-8 colon cancer cell WiDr. Isolation of the active compounds from the ethyl acetate fraction of C. gigantea root was carried out using Bioassay-guided Isolation method. Identification of active compounds was using NMR-1H, NMR-13C, HMBC, HMQC and UPLCMS/MS methods. The anticancer activity test of the identified compounds performed by using MTT method. The induction of apoptotic and cell cycle arrest evaluated by a flow cytometry method. The result of this study showed two active compounds were identified namely (1) (Pregnanon-5-en, 3,14,17 trihydroxy-12- (4’-cyclohexyl benzoate) -, (3β, 12β, 14β) - (9CI), (2) Pregn-5-en-20-one, 3,8,14-trihydroxy-12 - [(4’-hydroxy benzoyl) oxy] -, (3β, 12β, 14β, 17α) - (9CI). Both compounds inhibited the growth of colon cancer cell WiDr with IC50 values respectively were 15.89 μg/mL and 0.77 μg/mL. Both compounds increased the induction of apoptotic by increasing sub-G1, S, and G2-M following depletion of G0-G1 phase accumulation.

The purpose of this research was to test the anti-adipogenic activity and to identify the active compound of the leaf of Guazuma ulmifolia. The activity of anti-adipogenic of the compound of G. ulmifolia leaf was tested using primary cultures of Wistar strain white mouse preadipocytes. Isolation of the active compound was carried out in the following way. The powder of G. ulmifolia leaf was defated with n-hexane followed by extraction with 70% ethanol. The extract was concentrated and fractionated by liquid-liquid partition using chloroform and ethyl acetate solvents. The ethyl acetate fraction was loaded into a Vacuum Liquid Chromatography (VLC) followed by a reverse phase preparative layer chromatography to obtain a pure isolate. Isolated compound inhibited preadipocytes proliferation and differentiation. Intensive spectroscopic and spectrometric analysis suggested molecular structure of a tiliroside which agreed with previously reported data. The study successfully revealed the traditional claims of the anti-obesity agent of a leaf of G. ulmifolia through inhibition of preadipocytes proliferation and differentiation.

This research aims to find out the anticancer activity of ethanol extract from the roots, leaves, and flowers of Calotropis gigantea. This experiment was conducted by MTT method on T47D breast cancer cell line. The result showed that the root of Calotropis gigantea was more cytotoxic (IC50 89.76 μg/mL) on T47D breast cancer cell line than the leaves (IC50 459.51 μg/mL) and the flowers (IC50>1000). Based on the result, roots are potent to be chemotherapeutic agent, especially in breast cancer.

Drug development efforts to find new selective and safe drugs for cancer from natural resources are promising ones. The natural products are obtained in the multiple or single compounds. One of them is a sinensetin found in ethanol extract of Orthosiphon stamineus Benth. Sinensetin could inhibit cancer cell proliferation. However, it has a poor solubility so the absorption is low and then it impacts on the low bioavailability. The solubility problem in conventional drug could be solved by pharmaceutical manipulation. In the previous research, the manipulation was tried although there was no single compound found in the material tested. We found an optimal formula of a manipulation using solid disperse system of polyethylene glycol (PEG 6000) 15 times higher than sinensetin weight. This research was focused on observing the effect of the optimal formula of solid disperse system to inhibit cancer cell cycle. The cell lines used were T47D cells. The method used was flow cytometry. The result showed that the optimum formula has a consistent effect on the concentration of 40 and 60µg/mL. The sinensetin increase cell accumulation on S phase at the percentage of 18.80% (40µg/mL) and 22.21% (60µg/mL) compared to T47D normal cells. It reflects the S phase as the longest time experienced by the cells. Inhibition on S phase (S arrest) resulted from a DNA elongation. It causes an inhibition of DNA synthesis process. It could be concluded that the solid disperse of sinensetin was active to inhibit cancer cells proliferation on phase S. Keywords: cell cycle; sinensetin; solid disperse; poor solubility

Shiitake mushroom (Lentinus edodes) is one of the wood mushroom types that can be consumed as a food as well as for a medical purpose. Lentinan, a polysaccharide contained in shiitake, is well known for its use on cancer medication. Mycelium of Shiitake mushroom contains lentinan the same as other part of the mushroom like fruity body. Toxicity of the lentinan in mycelium compare to the fruity body has been first conducted by using Brine Shrimp Lethality Test (BST). Using Potato Dextrose Broth media with the growth rate of 3.88 percent did mycelium multiplications. Probit analysis showed that the toxicity of the mushroom’s cap, stem, and mycelium of Shiitake mushrooms is LC50 = 648.76507 mg/ml LC50 = 489.39444 mg/ml, and LC50 = 481.16941 mg/ml respectively.

The sponge Aaptos suberitoides can produce high secondary metabolite with some farmocological activities as antimicrobial, antiviral, antiinflamatory, and anticancer agents. The purpose of this research is to find out correlations between activities of the etanol extracts of marine sponges Aaptos suberitoides on the cancer growth of subcutaneous mice (Mus musculus) injected by Benzo(a)piren. For the purpose the mice were divided into six groups, i.e. I, II, III, IV, V, and VI. Each group was treated with carcinogenic inductions by intravenously injecting the Benzo(a)piren concentration of 0.3g/0.2 ml oleum olivarum. After the cancer was appeared at the fifteenth day, the mice were treated by the anticancer extracts of marine sponges Aaptos suberitoides with concentrations of 500 mg/kg BB (Group IV), 1000 mg/kg BB (Group IV), and 1500 mg/kg BB (Group IV). The treatments were orally done each day for two weeks. At the twentieth week, subcutaneous cancer tissues were taken to make histological preparates using a parafin method. Result of the histological observation indicates that cancer in the mice was fibrosarcoma characterized by the thickening dermis layers, necrosis, mitosis, and nuclear polymorphsm. Necrosis, mitosis, and nuclear polymorphism occurred in Groups II, IV, V, and VI, and did not in Groups I and II. Presentation of necrosis was 20-60%, mitosis was in 3-4 cells, and nuclear polymorphism was 100%. Result of the statistical analyses by using the Kruskal-Wallis method and the Pair Comparison test indicates that the anticancer extracts of marine sponges with the concentrations of 500 mg/kg BB, 1000 mg/kg BB, and 1500 mg/kg BB had no activity inducing mice skin cancer.

Chinaberry (Melia azedarach L., Meliaceae), a Mahogany family usually used as high quality timber, is native to Asia but now is found in other parts of tropical world continent. The leaves, fruits, bark, seed and root are use in traditional medicine and it has been shown to various pharmacological activities like antifungal, anti-malarial, antibacterial, hepatoprotective, anti-oxidant, anti-fertility, anthelmintic, antipyretic and cytotoxic. A review to its phytochemical and anticancer properties of M. azedarach and its sub species or varieties as an effort to analyze the literature on its developing used as anticancer agent. As results of literatures review indicates that fruit, bark, leaves, pulp and seed of Melia azedarach L. showed various in vitro cytotoxic activities in cancer cell lines, such as human colorectal carcinoma (HT-29), breast cancer (MCF-7, SK-BR-3), cervix hepatoma (HepG-2, SMMC-7721 and Hep3B), kidney epithelial cell (MDBK), human lung adenocarcinoma epithelial cell (A549), non-small cell lung cancer (H460), human lymphoblast lung (U937), human cancer promyelocytic leukemia (HL-60), AZ521 (stomach), human colon cancer (SW480), murine colorectal adenocarcinoma cell (CT26), human oral cancer cell (KB), human prostate cancer (PC3), liver (BEL7404), CNS (SH-SY5Y, U251, SF539), B16F10 mouse melanoma cell line; and showed various in vivo to adenocarsinoma mammary in C3H mice and mouse hepatocellular carcinoma H22 cells to BALB/c mice. Previous results suggested that cytotoxic organic compounds of Melia azedarach L. were supposed of flavonoids, triterpenoids (tirucallane), limonoids (meliarachin, meliatoxin B1, trichilin H, and toosendanin), steroids, and organic acids content compounds.

Objectives: This paper sought to understand and determine the cytotoxic’s effects of crude extract and its fraction from Calotropis gigantea leaves on human colon cancer WiDr cell lines.Methods: The ethanolic extract was fractionated gradually with certain substances to yield four fractions. The substances were dichloromethane, ethyl acetate, and butanol. The four fractions resulted in dichloromethane fraction, ethyl acetate fraction, butanol fraction, and a water fraction. These fractions were then investigated for their cytotoxic effects on WiDr cells. The cell viability was assessed using MTT colorimetric assay.Results: The result indicated that the cytotoxic effects of the ethanolic extract (IC5048.5 μg/ml), ethyl acetate fraction (IC5041.79 μg/ml), and dichloromethane fraction (IC5040.57μg/ml) produced a much more potent effect than the butanol fraction (IC50 737.74 μg/ml) and water fraction (IC508493 μg/ml).Conclusion: The ethanolic extract, ethyl acetate fraction and dichloromethane fraction exhibited a potent cytotoxic effect on human colon cancer WiDr cell line. The crude extract and fractions are potential to be developed as an anticancer agent in colon cancer therapy.

Andrographolide isolated from Andrographis paniculata Ness (Acanthaceae) at 0.35 mM , 0.70 mM and 1.40 mM induced DNA fragmentation and increased the percentage of apoptotic cells when TD-47 human breast cancer cell line was treated for 24 , 48 and 72 h. The results demonstrated that andrographolide can induce apoptosis in TD-47 human breast cancer cell line in a time and concentration-dependent manner by increase expression of p53, bax , caspase-3 and decrease expression of bcl-2 determined by immunohistochemical analysis. Keywords: Andrographis paniculata Ness , andrographolide, TD-47 cell , apoptosis.African Journal of Traditional and Complementary Medicine Vol. 4 (3) 2007: pp. 345-351

Ethyl p -methoxycinnamate, major ingredient of Kaempferia galanga rhizome, have been reported not only has analgesic – anti inflammatory activities like NSAIDs which inhibited cyclooxygenase, but also inhibit tumor cell proliferation in specimen of mouse epidermis. Therefore, it will be interesting to carry out synthetic studies on the derivates of ethyl p -methoxycinnamate and searching their citotoxic activity on WiDr cell. We wish to report of structure modification on carboxyl moiety of ethyl p -methoxycinnamate and evaluation on their citotoxic activity on WiDr cell. Isolation of ethyl p -methoxycinnamate from Kaempferia galanga rhizome was carried out by percolation with ethanol 96% as solvent. Hydrolysis of ethyl p -methoxycinnamate in basic condition was performed to obtain p -methoxycinnamic acid. Preparation of some thiourea derivates of ethyl p -methoxycinnamate was carried out by microwave irradiation. Citotoxicity assay was carried out by MTT method for 48 h. Modification of carboxyl group of ethyl p -methoxycinnamate to its thiourea form could be carried out by microwave irradiation gave; ( E )-3-(4-methoxyphenyl)- N -(phenylcarba- mothioyl)acrylamide (50%); ( E )-3-(4-methoxyphenyl)- N -(4-methoxyphenylcarbamothi- oyl)acrylamide (26%) and ( E )-3-(4-methoxyphenyl)- N -(4-methylphenylcarbamothioyl) acrylamide (54%), yield calculated for 2 step from the acid chloride. All compounds showed no citotoxic effect on WiDr cell at 48 h incubation. Keywords : ethyl p -methoxycinnamate, microwave irradiation, Kaempferia galanga , citotoxicity, WiDr cell