Kapulaga (Amomum cardamom) is one of herb which is commonly used for spices or medicine, especially the seeds. Previous studies showed that the essential oil of cardamom have antimicrobial, antiinflamatory, analgesic and antispasmodic activities. There was also evidence that A.cardamom has antiartherogenic and antidiabetic activity in rat. Despite the medicinal benefits of A.cardamom, this herb is not yet standardize for herb medicine. For its standardization, A.cardamom has to pass the preclinical and clinical studies to ensure its efficacy and safety profile. The aims of this study was to examine the safety profile of A.cardamom seed extract based on renal parameter function (ureum and creatine levels). Acute toxicity test was conducted based on the OECD 420 Fixed Dose Prosedure guideline that consists of two test steps, preliminary and main tests. For preliminary test, initially with 300 mg/kg BW dose of A.cardamom seed extract, followed by 2000 mg/kg BW. The main test consists of control and treatment group and each group used 5 rats. The rats in both groups were given 2000 mg/kg BW in a single dose of A.cardamom seed extract. The ureum and cretainine levels were assessed at day 14th using an enzymatic-photometric method. The data were analyzed by independent sample test. The results revealed that the ureum and creatinine levels in control and treatment groups were not statistically different. The mean of ureum levels in the control and tretment groups were 47.24±6.18 and 43.98±6.78 (p=0.45) and the mean of creatinine levels were 0.43±0.04 and 0.36±0.12 (p=0.31) respectively. These results show that a high single dose of A.cardamom seed extract (2000 mg/kgBW) did not toxic in rat based on renal function parameters.

Cervival cancer is one of the top rank of gynecological malignancy in the world, leading to high morbidity and mortality rates. Cisplatin is a chemotherapeutic agent that is generally used to treat cervical cancer but the use of this drug is limited because of serious side effects. Metformin, a diabetic drug, decreases not only blood glucose levels but also cell viability of some cancer cells. The aim of this study was to investigate the anti-proliferative effect of combination metformin and cisplatin in HeLa cells (cervical cancer cell line). Anti-proliferative effect of these combined drugs was analized using MTT assay, combination index assay and HeLa cell morphology. Inhibitory concentration (IC 50) of cisplatin and metformin was determined before performing combination index assay. Administration of 10 mM metformin showed inhibition of HeLa cell proliferation and it reached 50% inhibition of cell proliferation at 60 mM. Whilst, cisplatin showed a stronger anti-proliferative effect with initial inhibition dose at 12 µM and IC 50 dose at 44 µM. Combination of 30 mM metformin and 5 µM cisplatin indicated the strongest anti-proliferative effect on HeLa cell. In conclusion, metformin may become a promising drug for treatment of cervical cancer in future which enhances anti-proliferative effect of cisplatin.

No abstract

One-third of the Indonesian population uses herbs for alternative medicine empirically. One of them is Kapulaga (Amomum cardamomum) which known as a spice and traditionally used for the treatment of rheumatic, fever, cough, sore throat, and mouth odor. The clinical use of herbs must be supported by scientific evidenced-based and its safety profile. The risk of exposure to a substance in humans can be identified through the toxicity tests on animals. The liver histopathological structure is one of the parameters of the acute toxicity test. This study to determine the acute toxicity of Kapulaga seeds extract (Amomum cardamomum) based on the liver histopathological structure of Wistar rats. The sample selection based on inclusion and exclusion criteria in the OECD 420 guideline. The research consisted of a preliminary and the main test. One rat was used in the preliminary test with an initial dose of cardamom seed extract 300 mg/kg BW and followed by a maximum dose of 2000 mg/kg BW after 48 hours. The main test used 10 rats that were randomly divided into control and treatment groups. Based on the result of the preliminary test, the treatment group was given a single dose of cardamom seed extract 2000mg /kg BW, whilst the control group was given distilled water. Observations of any toxic signs or dead were conducted every 30 minutes in the first 4 hours and continued once per day until 14thday. Assessment of the degree of liver damage was done using the liver damaged scoring and compared using the Mann Whitney test (α = 0.05). The average liver damage score of control and treatment groups is 0.96 ± 0,856 and 0.96 ± 0,604, respectively, and did not show any statistically significant differences (p>0,05). Kapulagaseeds (Amomum cardamomum) had no acute toxic effect based on the liver histopathological structure of Wistar rats.

The herb frequently used as spices or remedies in the Indonesian community, with the seed as the most common part is kapulaga (Amomum cardamomum). According to earlier evidence, this possessed antibacterial, antifungal and several biological properties, reduced blood glucose and atherogenic parameter, and is developed as standardized herbal cures. However, the application of herbal medicine requires validating evidence of safety and effectiveness, including toxicity tests, particularly in clinical settings. The target organs in this comprised hepar, due to the role in several drug metabolism. This study aimed at discovering the safety profile of kapulaga seed extract based on the hepatic transaminase enzyme (SGOT and SGPT) level, by conducting an acute toxicity test in Winstar rats. Also, this was implemented with the OECD 420 Fixed-Dose Procedure, and the preliminary test employed 300 mg/kg BW dose followed by a maximum single quantity (2000 mg/kg BW) of kapulaga. The main test was executed by a separation into control and treatment groups of 5 rats each. Therefore, a single dose of 2000 mg/kg BW kapulaga seed extract was administered to the treatment group, while the control group received standard pellets and water ad libitum. The blood from orbital vein was acquired on day 14, and SGOT and SGPT were subsequently assessed by an enzymatic-photometric method. Also, this data was analyzed using an independent sample t-test, and the mean of SGOT in both groups were 116.92±22.35 and 98.02±16.38 (p=0.17), with 58.72±8.79 and 47.64±7.30 (p=0.06) as SGPT respectively. Therefore, there was no statistical difference, and no acute toxicity signs were discovered. The maximum dose was not toxic and did not result in poisonous symptoms or alter hepatic transaminase enzyme (SGOT and SGPT) in rats.Keywords: Amomum cardamomum, kapulaga, acute toxicity, SGOT, SGPT  Uji Toksisitas Akut Ekstrak Biji Kapulaga (Amomum cardamomum) Berdasarkan Kadar Enzim Transaminase Hepar Tikus WinstarAbstrakKapulaga (Amomum cardamomum), merupakan salah satu herbal Indonesia yang secara umum dimanfaatkan sebagai rempah-rempah maupun obat, terutama bagian biji. Beberapa bukti sebelumnya menunjukkan bahwa kapulaga memiliki berbagai aktivitas biologis seperti antibakteri, antijamur, dan sudah dibuktikan mampu menurunkan glukosa darah dan parameter arterogenik. Bukti tersebut mendukung pengembangan kapulaga sebagai obat herbal terstandar. Penggunaan obat herbal terutama di klinik harus didukung dengan adanya bukti keamanan maupun efektivitasnya termasuk uji toksisitas. Hepar merupakan salah satu target organ dari uji toksisitas karena perannya yang penting pada metabolisme sebagian besar obat. Penelitian ini bertujuan untuk menilai profil keamanan ekstrak biji kapulaga melalui uji toksisitas akut menggunakan tikus Winstar berdasarkan kadar enzim transaminase hepar (SGOT dan SGPT). Uji toksisitas akut berpedoman pada OECD 420 Fixed Dose Procedure. Uji pendahuluan menggunakan ekstrak biji kapulaga dosis 300 mg/kg BB dan diikuti dengan dosis tinggi 2000 mg/kg BB yang diberikan secara tunggal. Uji utama dilakukan dengan membagi tikus ke dalam kelompok kontrol dan perlakuan, masing-masing kelompok terdiri atas 5 tikus. Berdasarkan hasil uji pendahuluan, uji utama menggunakan dosis tunggal 2000 mg/kg BB untuk kelompok perlakuan, sedangkan kelompok kontrol hanya mendapatkan pelet dan air secukupnya. Pada hari ke-14, darah dari vena orbital diambil, lalu kadar SGOT dan SGPT diukur menggunakan metode enzymatic-photometric. Independent sample t-test digunakan untuk menilai data rata-rata kadar SGOT dan SGPT dari kedua kelompok. Rata-rata kadar SGOT pada kelompok kontrol dan perlakuan sebesar 116,92±22,35 dan 98,02±16,38 (p=0,17), sedangkan rata-rata SGPT sebesar 58,72±8,79 dan 47,64±7,30 (p=0,06). Perbedaan rata-rata SGOT dan SGPT pada kedua kelompok tersebut secara statistik tidak bermakna dan tidak ditemukan tanda toksisitas pada semua hewan coba. Ekstrak biji kapulaga dosis maksimal 2000 mg/kg BB tidak toksik pada hepar tikus karena tidak menimbulkan tanda toksisitas maupun mengubah enzim transaminase hati (SGOT dan SGPT). Kata kunci: Amomum cardamomum, kapulaga, toksisitas akut, SGOT, SGPT