Common Traditional Medicine Research Articles

Biological Activities of Deer Antler-Derived Peptides on Human Chondrocyte and Bone Metabolism.

Orally administered "tortoiseshell and deer antler gelatin" is a common traditional medicine for patients with osteoporosis or osteoarthritis. From the pepsin-digested gelatin, we previously isolated and identified the osteoblast-stimulating pentapeptide, TSKYR. Its trypsin digestion products include the dipeptide YR, enhancing calcium ion uptake, and tripeptide TSK, resulting in remarkable 30- and 50-fold increases in mineralized nodule area and density in human osteoblast cells. These peptides were chemically synthesized in this study. The composition of deer antler preparations comprises not only proteins and peptides but also a significant quantity of metal ion salts. By analyzing osteoblast growth in the presence of peptide YR and various metal ions, we observed a synergistic effect of calcium and strontium on the effects of YR. Those peptides could also stimulate the growth of C2C12 skeletal muscle cells and human chondrocytes, increasing collagen and glycosaminoglycan content in a three-dimensional environment. The maintenance of bone homeostasis relies on a balance between osteoclasts and osteoblasts. Deer antler peptides were observed to inhibit osteoclast differentiation, as evidenced by ROS generation, tartrate-resistant acid phosphatase (TRACP) activity assays, and gene expression in RAW264.7 cells. In summary, our findings provide a deep understanding of the efficacy of this folk medicine.

Chemical characterization of different parts of Forsythia suspensa and α-glucosidase and pancreatic lipase inhibitors screening based on UPLC-QTOF-MS/MS and plant metabolomics analysis

Forsythia suspensa (Thunb.) Vahl (FS) is an important plant with high edible and medicinal values. The edible fruit of FS is a common traditional medicine in China, Japan and Korea. Compared to the research on the phytochemistry and pharmacology of the fruits, study on the other parts of FS, such as leaves and flowers is still limited. In this study, an integrated strategy based on ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS), plant metabolomics and correlation analysis was established for comprehensively chemical characterization of fruits, leaves and flowers of FS, and discovery of α-glucosidase and pancreatic lipase inhibitory metabolites. The plant metabolic profiling of fruits, leaves and flowers of FS was performed by UPLC-QTOF-MS/MS, and a total of 74 secondary metabolites, including 15 phenylethanoid glycosides, 20 lignans, 10 cyclohexanol derivatives, 11 organic acids, 9 flavonoids, 3 triterpenes, and 10 other compounds were identified. Then, 29 differential secondary metabolites that responsible to distinguish the fruits, leaves and flowers of FS were further screened out by multivariate statistical analysis. Meanwhile, the α-glucosidase and pancreatic lipase inhibition of different parts of FS were evaluated and compared by in vitro experiments. The results demonstrated that the leaves of FS showed the highest inhibition on α-glucosidase and pancreatic lipase with IC50 of 0.17 ± 0.04 mg/mL and 0.56 ± 0.33 mg/mL, respectively. Then, the correlation between differential metabolites and enzyme inhibitory activities were investigated by Pearson correlation analysis, and 12 potential α-glucosidase and pancreatic lipase inhibitors were screen out. Additionally, the α-glucosidase and pancreatic lipase inhibitory activities of five potential enzyme inhibitory components, including quercitrin, rutin, kaempferol-3-O-rutinoside, pinoresinol-4-O-glucoside and phillyrin were further validated by in vitro assays and molecular docking analysis. The results showed that all the five potential inhibitors showed good inhibitory effects on α-glucosidase and pancreatic lipase, and the binding of the five inhibitors to enzymes mainly through hydrogen bonding, hydrophobic force, and ionic bonding. This study provided a feasible strategy for comparison and discrimination of different parts of medicinal plant and discovery of bioactive components, and also provided useful information for future utilization of different parts of FS.

Awareness and Attitude of Parents and Caregivers Regarding Harmful Traditional Medical Practices Towards Children in Aseer Region of Saudi Arabia.

Traditional medicine has potential benefits, but distinguishing safe from risky procedures is crucial for safeguarding children's health. Harmful practices in Aseer Region of Saudi Arabia, deeply rooted in cultural heritage, require scrutiny of parental attitudes and awareness. The study aims to investigate and analyze the awareness, attitudes, and associated factors contributing to Harmful Traditional Medical Practices towards children in Aseer Region of Saudi Arabia. This study employed a cross-sectional design, using an online survey to collect data via a structured questionnaire developed from an extensive literature review on harmful traditional child medical practices in Aseer Region of Saudi Arabia. The study found that most respondents were aged 41-49 years (42.4%), lived in cities (77%), had at least an undergraduate degree (50.1%), and favored traditional medicine (55.9%). Common traditional medicine choices included "Herbs" (28.4%) and "Belly massage" (27.6%). Age significantly affected treatment preferences, while "Place of Resident" and "Education Level" hinted at potential differences. Personal experiences (37.2%) and family networks (31.4%) were key sources of information. Logistic regression analysis uncovered intricate links between sociodemographic and traditional medicine practices. Respondents' views on "Awareness", "Effectiveness", and "Complications" demonstrated notable statistical significance, influencing parents' and caregivers' perspectives in the study. The study's outcomes underscore the imperative for heightened awareness and education concerning the potential hazards and complications tied to harmful traditional medical practices among parents and caregivers in Aseer Region of Saudi Arabia, particularly with regard to their children's well-being. The evident inclination towards traditional medicine, reliance on personal experiences and familial networks for healthcare insights, and reservations regarding contemporary medical approaches underline the significance of addressing cultural beliefs.

Methods of Processing Medicinal Plants: A Semantic Study of the Use of Verbs in Sesotho Sa Leboa

From time immemorial, medicinal plants have been common traditional medicines for treating diseases and ailments in most households. Even today, plants are used for treating ailments and diseases such as the flu and coronavirus disease 2019 (COVID-19). This article investigates the semantic use of verbs for collection, preparation and administration as methods of processing medicinal plants in Sesotho sa Leboa. Most of the medicinal plants, like folktales, are extinct, so by writing this study the ethnobotanical knowledge of the communities will be promoted and preserved. Medicine from medicinal plants is mostly used in a traditional medical healthcare system. Recent studies have indicated how the medicinal plants form the foundation of traditional medicine and how these are sometimes incorporated into allopathic or biomedical medicine. For the medicinal plant to attain its medicinal value, several processes take place and verbs are used to describe them (processes). Specific meaning is attached to the verbs of methods used during the collection, preparation and administration of medicinal plants. Ethnobotanical theory forms the framework of this article, supported by the theory of linguistics. A qualitative approach is used to explain concepts in the collection, interpretation and analysis of data. Data is collected from existing documents and auto-ethnography. The study found that verbs used in the methods of processing medicinal plants are semantically used in relation to specific parts of the plant.

Ethnobotanical survey of plants used by the riparian population of Banco National Park (Abidjan, Ivory Coast)

Abstract. Gnahore E, Kouadio KR, Amba AJG, Kone M, Bakayoko A. 2022. Ethnobotanical survey of plants used by the riparian population of Banco National Park (Abidjan, Ivory Coast). Asian J Ethnobiol 5: 121-129. Situated at the "heart" of Abidjan, Banco National Park (BNP), Ivory Coast, is the rare relics of moist, dense rainforests coveted everywhere. This work was undertaken with an aim of identifying the plants most usually used by the riparian population of BNP in human food, animal food, and pharmacopeia. An ethnobotanical survey was carried out of the riparian population of the BNP. The method consists of an ethnobotanical survey realized among the inhabitants of the park and those of the surrounding urban districts. The method used was semi-structured interviews. This study targeted 294 people, including 20% men and 80% women, aged between 30 and 60. A total of 36 plant species from 34 genera and 28 families were recorded. Thirteen species were used in food, three fodder species, and thirty others used to treat several ailments in the area. Two of these plants have strong ratio utilization in human food: Myrianthus arboreus P.Beauv. (15.25%) and M. libericus Rendle (14%). Thus, in the area study, five species are respectively considered threatened and three species rare. Leaves (32.55%) and bark (20.93%) are the most used organ. Decoction (98%) was the most common traditional medicine preparation method. Indigenous knowledge distribution in the community showed significant differences (p<0.05) in the study groups for factors of age, sex, gender, and educational level. The number of resources used can seriously impact the forest negatively. It is urgent to adopt a lasting management plan for sustainable harvest for the safeguard and preservation of the plant cash of the BNP.

Traditional medicine trade and uses in the surveyed medicine markets of Western Kenya.

There exist vast traditional medicine and herbal remedies prescribed for diseases and socio-cultural ills that are sold in local medicine markets. To assess the common traditional medicine traded in the local medicine markets and used for treating common diseases. The study was carried out in nine purposively selected medicine markets spread out in seven administrative counties of Western Kenya. Purposive sampling with elements of snow ball method was employed in the identification of willing respondents. In addition, face to face interviews were conducted with the aid of a pre-tested semi-structured questionnaire that sought to extract a targeted and expertise information from the respondents. The survey recorded 45 commonly traded plant families composed of 78 genera and 87 medicinal plant species. Meliaceae, Apocynaceae and Fabaceae were leading plant families whereas Trichilia emetica, Azadirachta indica, Dregea schimperi and Aloe spp. were commonly traded. Traditional medicine traded in the local medicine markets continue to play a significant role in the treatment of common diseases. Frequently traded medicinal plant species should be prioritized for conservation.

Potential Inhibitory and Inducing Effects of Triphala Formulation on Cytochrome P450 Enzymes

Triphala formulation is one of the most common traditional medicines used for several health conditions. The study aimed to investigate the inhibitory and inducing potentials of Triphala formulation, including its active compounds gallic acid and ellagic acid, on cytochrome P450 (CYP450) enzymes. The inhibitory effects of Triphala formulation, gallic acid and ellagic acid on the 5 major human CYP450 enzymes were evaluated using a bioluminescent CYP450 inhibition assay. Evaluation of inducing effect of Triphala formulation on CYP1A2 and CYP3A1 mRNA expression following daily oral doses of 1,000 and 5,000 mg/kg body weight for 28 days was evaluated using RT-PCR. Gallic acid potently inhibited CYP1A2, CYP2C9 and CYP2C19 with a non-competitive nature, while the inhibitory potencies on CYP2D6 and CYP3A4 were weak. Chronic dosing of Triphala formulation at 1,000 and 3,000 mg/kg body weight significantly induced mRNA expression of CYP1A2 but not CYP3A1. Results suggest the propensity of metabolic drug interactions when Triphala formulation was concurrently administered with other conventional drugs or herbal medicines. 
 HIGHLIGHTS
 
 Gallic acid potently inhibited CYP1A2, CYP2C9 and CYP2C19 with a non-competitive nature
 Triphala formulation at the dose of 1,000 and 3,000 mg/kg body weight significantly induced mRNA expression of CYP1A2
 Results suggest the propensity of metabolic drug interactions when Triphala formulation is concurrently administered with conventional drugs or herbal products by human CYP450 enzymes, particularly CYP1A2, CYP2C9 and CYP2C19
 
 GRAPHICAL ABSTRACT

Wound Healing by Italian and Algerian Resins

Wound Healing by Italian and Algerian Resins

English

Triphala formulation is one of the most common traditional medicines used for several health conditions. The study investigated the pharmacokinetics of gallic acid following an oral dose administration in rats. The pharmacokinetics of gallic acid was investigated in rats following a daily oral dose of 1,000 and 5,000 mg/kg body weight (28 days). Plasma concentrations of gallic acid were measured using liquid chromatography-mass spectrometry (LC-MS/MS). Non-compartmental pharmacokinetic analysis approach was applied for data analysis. The pharmacokinetics was linear without dose-dependent characteristics. Gallic acid was rapidly absorbed, reaching maximum concentration within 1 h and was also rapidly cleared from rat systemic circulation within 12 h of administration. The pharmacokinetics of gallic acid was linear with about 5-fold increase in Cmax and systemic exposure AUC0- when the dose was increased from 1,000 to 5,000 mg/kg body weight. The pharmacokinetics of gallic acid following both regimens was similar. Terminal phase elimination half-life (t1/2z), apparent volume of distribution (Vz/F) and total clearance (CL/F) ranged from 0.7-1.7 h, 327-1,159 L and 195-607 L/h/kg. The pharmacokinetics of gallic acid obtained from the present study in rats provides preliminary information for designing proper pharmacokinetic studies in humans for further dose optimization of appropriate dosage regimens of Triphala formulation for treatment of various diseases or health conditions. Key words: Triphala formulation, pharmacokinetics, gallic acid.

In Vitro Anticancer Activity and Oxidative Stress Biomarkers Status Determined by Usnea barbata (L.) F.H. Wigg. Dry Extracts.

Lichens represent an important resource for common traditional medicines due to their numerous metabolites that can exert diverse pharmacological activities including anticancer effects. To find new anticancer compounds with fewer side effects and low tumor resistance, a bioprospective study of Usnea barbata (L.) F.H. Wigg. (U. barbata), a lichen from the Călimani Mountains (Suceava county, Romania) was performed. The aim of this research was to investigate the anticancer potential, morphologic changes, wound healing property, clonogenesis, and oxidative stress biomarker status of four extracts of U. barbata in different solvents (methanol, ethanol, acetone, and ethyl acetate), and also of usnic acid (UA) as a positive control on the CAL-27 (ATCC® CRL-2095™) oral squamous carcinoma (OSCC) cell line and V79 (ATCC® CCL-93™) lung fibroblasts as normal cells. Using the MTT assay and according to IC50 values, it was found that the most potent anticancer property was displayed by acetone and ethyl acetate extracts. All U. barbata extracts determined morphological modifications (losing adhesion capacity, membrane shrinkage, formation of abnormal cellular wrinkles, and vacuolization) with higher intensity in tumor cells than in normal ones. The most intense anti-migration effect was established in the acetone extract treatment. The clonogenic assay showed that some U. barbata extracts decreased the ability of cancer cells to form colonies compared to untreated cells, suggesting a potential anti-tumorigenic property of the tested extracts. Therefore, all the U. barbata extracts manifest anticancer activity of different intensity, based, at least partially, on an imbalance in antioxidant defense mechanisms, causing oxidative stress.

Methanol Extract of Usnea barbata Induces Cell Killing, Apoptosis, and DNA Damage against Oral Cancer Cells through Oxidative Stress.

Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially for oral cancer cells. The aim of this study was to investigate the cell killing function of methanol extracts of U. barbata (MEUB) against oral cancer cells. MEUB shows preferential killing against a number of oral cancer cell lines (Ca9-22, OECM-1, CAL 27, HSC3, and SCC9) but rarely affects normal oral cell lines (HGF-1). Ca9-22 and OECM-1 cells display the highest sensitivity to MEUB and were chosen for concentration effect and time course experiments to address its cytotoxic mechanisms. MEUB induces apoptosis of oral cancer cells in terms of the findings from flow cytometric assays and Western blotting, such as subG1 accumulation, annexin V detection, and pancaspase activation as well as poly (ADP-ribose) polymerase (PARP) cleavage. MEUB induces oxidative stress and DNA damage of oral cancer cells following flow cytometric assays, such as reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) production, mitochondrial membrane potential (MMP) depletion as well as overexpression of γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG). All MEUB-induced changes in oral cancer cells were triggered by oxidative stress which was validated by pretreatment with antioxidant N-acetylcysteine (NAC). In conclusion, MEUB causes preferential killing of oral cancer cells and is associated with oxidative stress, apoptosis, and DNA damage.

A cross-sectional study to determine the use of alternative medicines during pregnancy in the district hospitals in Manicaland, Zimbabwe.

Traditional medicines are widely used in the rapidly growing health system and are of economic importance. The study aimed at determining the frequency, pattern of use and factors that influence traditional medicines use during pregnancy. A cross-sectional study was carried out at four district hospitals in Manicaland, Zimbabwe, using questionnaire based convenience sampling. Traditional medicines use was found to be high with 54% (n = 337) of pregnant women using traditional medicines during pregnancy. The major purpose of use of traditional medicine was found to be preparation for delivery; cervical dilation in particular. The following factors showed a significant statistical association for use of traditional medicines: previous mode of delivery (p = 0.006), level of education (p = 0.016), family income (p = 0.007), and residential settlement (p =0.026). Some of the common traditional medicines used during pregnancy include Camellia sinensis, Aloe, Spirostachys Africana, Thumbergia lancifolia, Dalbergiella nyasae, Steganotaenia oraliacea, Stomatostemma monteiroae and Cussonia arborea. A number of pregnant women use traditional medicines as partus preparators (labour aids) throughout the entire pregnancy period. This calls for obstetricians, general practitioners and midwives to inquire about use of traditional medicine in history.

Efek kurkumin sintesis dan Pentagamavunon-0 terhadap Produksi Progesteron Kultur Sel Luteal dengan Pemberian Forskolin

Curcumin is one of the common traditional medicines that is often used for fertility regulation. Curcumin analogue, pentagamavunon-0/PGV-0, exerted similar effect with curcumin. Synthetic curcumin and PGV-0 possesses molecular structures similar to prostaglandin. It has been reported that luteal cells are able to produce progesterone in vitro by addition of several hormones such as LH and prostaglandin F2? (PGF2?). Stimulation of luteal cell cultures with LH and/or PGF2? in the presence of synthetic curcumin and PGV-0 will interfere with the progesterone production. Nevertheless, the precise site of action of curcumin remains unknown. The present study aims to determine the effect of synthetic curcumin and PGV-0 on the progesterone production by luteal cell cultures in the presence or absence of several known stimulators or inhibitors sucs as LH, PGF2? and forskolin, respectively. The results indicated that synthetic curcumin reduced the progesterone concentration significantly (p<0,05) in the luteal cell culture treated with solvent, LH and/or PGF2?, in the presence or absence of forskolin. In the groups treated with PGV-0, and induced with LH and/or PGF2?, the concentration of progesterone did not change significantly (p>0,05). Addition of forskolin on the control group resulted in higher progesterone concentration as that of LH. The findings indicated that synthetic curcumin inhibits progesterone production by the luteal cell cultures through the cAMP/PKA/MAP-Kinase signaling cascade, but PGV-0 might have the site of action in the PLC/PKC/MAP-Kinase signaling cascade.

Ethnomedicinal Resources of the Indigenous People’s (IP) Groups in the SOCSARGEN Region

An ethnomedicinal study was conducted to document the medicinal plants used, the manner of preparation and application in the treatment of ailments and the consensus in the use of medicinal plants to treat various ailments among four (4) indigenous people's groups, the Obo in Lake Sebu, South Cotabato, T'boli in Maitum, Sarangani Province, and Blaan and Tagakaolo in General Santos City. The ethnobotanical interview was conducted using open-ended semi-structured questionnaires among identified traditional healers and elders as well as the household in the community. A total of 136 plants species, mostly herbs (47%), have been recorded with the corresponding conditions or illnesses in which they are believed to exert a therapeutic effect. Plant parts utilized for traditional medicine of the 4 IP groups include leaves (38%), roots (25%) and bark/stem (16%). Decoction (54%) and direct consumption (27%) applied via oral route are the common traditional medicine preparation. The IP communities in the SOCSARGEN Region have a rich pharmacopeia of traditional medicinal plants that persist through time despite the availability and convenience offered by modern medicine.
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Population-based comparison of traditional medicine use in adult patients with allergic rhinitis between South Korea and Taiwan

BackgroundAs the number of people seeking to use traditional medicine to treat common diseases is increasing worldwide, the quantity of information that needs to be analyzed is also increasing. Traditional medicine is commonly used in South Korea and Taiwan for treating allergic rhinitis and is covered by the National Health Insurance in both countries. To date, there has been no nationwide comparison of traditional medicine used to treat patients with allergic rhinitis between these two countries. MethodsThis study analyzed the National Health Insurance cohort database in 2011 from South Korea and Taiwan to compare the utilization pattern of traditional medicine in adult patients with allergic rhinitis. ResultsDuring 2011, there were significantly more adult patients with allergic rhinitis using traditional medicine in Taiwan (9898/54,555, 18.1%) than in South Korea (533/11,761, 0.5%). Users of traditional medicine from both countries were more prevalent among women, the younger population aged 20–39 years, and among people who visited traditional medicine clinics more frequently than hospitals. The most common traditional medicine treatment modality for allergic rhinitis was acupuncture in South Korea, while powdered herbal preparations was most commonly used in Taiwan. Xiaoqinglong-tang (Socheongryongtong-tang) was the most commonly used herbal preparation in South Korea, while Xinyi-san (Sinyi-san) was the most commonly prescribed herbal preparation in Taiwan. ConclusionAn analysis of the National Health Insurance database of South Korea and Taiwan revealed different utilization patterns of traditional medicine in adult patients with allergic rhinitis between the two countries. We believe these phenomena are due to the difference in the national healthcare systems in both countries.

The Utilization of Traditional Medicine to Treat Fever in Children in Western Javanese Culture

ABSTRACTFever regularly affects toddlers and may make their parents uneasy. This study aimed to identify common traditional medicines used by parents to treat their children’s fever at home. The study was conducted in Karyasari, Leuwiliang, Bogor District. It was descriptive in design, and the instrument used was a questionnaire developed by the authors. A group of 106 respondents was selected through the cluster sampling method. All respondents were female; the youngest was 20 years old, and the oldest was 53 years old. The majority of respondents had graduated from elementary and junior high school (93%), were currently unemployed (95%), and had a household income of less than Bogor’s regional minimum wage (RMW) (91%). The majority of mothers (90.6%) identified fever through tactile perception. The most common traditional medicines used by respondents were onion (86.8%) mixed with oil (64.2%) and applied to the body (86.8%). The results of this study suggested the need for health education concerning the use of traditional medicine to treat fever.

Gentiana lutea Linn. (Yellow Gentian): A comprehensive review

Gentiana lutea Lin. commonly known as yellow gentian, bitter root and bitterwort belonging to family Gentianaceae is a common traditional medicine freely available in hilly areas in Japan, Europe and adjoining continents, its medicinal properties are also mentioned in Ayurveda. The plant is reported to posse’s antioxidant, antifungal, anti-inflammatory, stomachic, appetizer and immunomodulatory properties etc.Gentiana lutea is an important source of bitter phytoconstituents such as amarogentin, gentiopicrinor gentiopicroside, gentiolutelin and its dimethyl acetal, gentioluteol, gentanine, amaroswerin, gentioside including a new iridoid named gentiolutelin. Traditionally the plant is used as stomachic tonic, bitter tonic, dyspepsia, gastric inefficiency in infants, digestive tonic, catarrhal diarrhoea, anaemia, malarial disease etc. The present review is an effort to generate an interest among the mosses regarding its immense potential in preventing and treating several diseases.

Phytochemical investigation of abietanoid quinones: extraction, structure elucidation, toward systhesis in the laboratory

The rootes of Chinese sage, Salvia miltiorrhiza Bunge (labieteae) are used to prepare an important traditional medicine in the Chinese pharmacoepia, Dan Shen. Indeed, related members of this genus are common traditional medicines throughout the world, making Salvia species the targets of intense phytochemical investigations. The active constituents of these species have been reported to be several abietanoids diterpenes bearing o-quinone or p-quinones. In this report we will present results of our investigation of Salvia species alogwith thesynthesis of some active structures

Traditional medicine as an alternative form of health care system: A preliminary case study of Nangabo sub-county, central Uganda

This study was conducted in Nangabo sub-county of Wakiso district. The purpose was to document the common Traditional Medicine (TM) practices; assess the local people's preferences for TM versus western medicine (WM) and lastly to determine the awareness about the importance of TM by local people. Data were collected using semi-structured administered face-to-face with respondents. A total of 120 interviewed. Six focused group discussions (FGDs) were held to validate the questionnaire responses. Data were analyzed descriptively using Statistical Package for Social Sciences (SPSS). The findings indicated that most (43%) respondents derive their livelihoods from traditional medicine practices. Three forms of TM were reported-herbalism (67%), spiritual counseling (23%) and bone setting (10%). Although the majority (81%) of respondents were quite aware of the importance of TM in the sustenance of health care system, majority (55%) of them shunned TM in preference to WM, largely because of the belief that TM is evil-founded and devilish in nature. Only 45% of the respondents preferred TM to WM. The main reasons given for visiting TM practioners rather than western medical practitioners were that TM is sometimes more effective than WM and that in many instances it has very minimal side effects on the human body. There is, however, a need for Ugandan government to legitimize the practice of TM since it contributes a lot to health care needs in areas where western medicine is insufficiently provided. In addition, there is a need for further research into the efficacy and safety of traditional medicines if it is to be adequately integrated into western medicine.