Antidiabetic Stilbene and Anthraquinone Derivatives from Rheum undulatum

Choi Sang Zin,Lee Sung Ok,Jang Ki Uk,Chung Sung Hyun,Park Sang Hyun,Kang Hee Chol,Yang Eun Young,Cho Hi Jae,Lee Kang Ro The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.9

The antidiabetic-activity-guided fractionation and isolation of the $80\%$ EtOH extracts obtained from cultivated Korean Rhubarb rhizomes (Rheum undulatum, Polygonaceae) led to the isolation and characterization of one stilbene, desoxyrhapontigenin(1) and two anthraquinones, emodin (2) and chrysophanol (3). Their structures were established by chemical and spectroscopic methods. Compounds 1, 2, and 3 inhibited postprandial hyperglycemia by 35.8, 29.5, $42.3\%$, respectively.

A role of <i>Ficus</i> species in the management of diabetes mellitus: A review

Deepa, Ponnuvel,Sowndhararajan, Kandhasamy,Kim, Songmun,Park, Se Jin Elsevier 2018 Journal of Ethnopharmacology Vol.215 No.-

<P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>Diabetes mellitus is one of the most common global health concerns, with a rapidly increasing incidence. A variety of medicinal plants, particularly those belonging to the genus <I>Ficus</I> (Moraceae), and their active compounds have been used to treat diabetes and related chronic disorders since ancient times.</P> <P><B>Aim of the study</B></P> <P>The aim of this review is to provide information regarding traditional and scientific knowledge of <I>Ficus</I> species with antidiabetic activity to researchers.</P> <P><B>Materials and methods</B></P> <P>A literature search was conducted to obtain information about the antidiabetic properties of <I>Ficus</I> from the electronic databases. Common and scientific names of various <I>Ficus</I> species were used as keywords for the search, along with the terms antidiabetic, hypoglycemic and diabetes.</P> <P><B>Results</B></P> <P>Among the assorted species of <I>Ficus</I> that were included in our search, <I>F. benghalensis</I>, <I>F. carica</I>, <I>F. glomerata</I>, <I>F. glumosa</I>, <I>F. racemosa</I>, and <I>F. religiosa</I> exhibited remarkable antidiabetic properties with various mechanisms of action. Moreover, <I>Ficus</I> species are versatile sources of bioactive metabolites such as flavonoids, phenolic acids, tannins, alkaloids, glycosides, coumarins, triterpenoids, sterols and vitamin E. These extracts and isolated compounds significantly have enhanced insulin secretion and subsequently reduced blood glucose level in various <I>in vivo</I> studies.</P> <P><B>Conclusion</B></P> <P>This review summarizes the antidiabetic potentials of the genus <I>Ficus</I>, including pharmacological studies with mechanisms of action as well as ethnobotanical uses. This review can help inform future scientific research towards the development of novel antidiabetic drugs.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Streptozotocin 유도 당뇨병 생쥐 모델에서 지각 추출물의 항당뇨 효과

이경재,임지성,김지은,이수경,김현주,송용선 한의병리학회 2023 동의생리병리학회지 Vol.37 No.1

The aim of this study is to evaluate the antidiabetic effect of the water extract of Aurantii fructus immaturus (WAF), in diabetic models using enzyme, cells and mice, and to suggest a putative mechanism explaining its antidiabetic effect. In an enzyme model using the enzyme α-glucosidase, WAF had no significant effect on α-glucosidase, as compared with acarbose, an antidiabetic drug. Nonetheless, WAF was capable of reducing the blood glucose levels during oral sucrose tolerance test and oral glucose tolerance test, implying that there would be other antidiabetic pathways in no relation to inhibition of α-glucosidase. In cell models using RIN-m5f β-cells and L6 myotubes, WAF, at its non-cytotoxic doses, augmented the secretion of insulin in RIN-m5f β-cells stimulated with 5 mM glucose. In addition, it enhanced the cellular uptake of glucose in L6 myotubes stimulated with deprivation of glucose for 12 h. Therefore, it is most likely that WAF may exert its antidiabetic effects, at least in part, by enhancing insulin secretion and glucose uptake. Meanwhile, in diabetic mice induced with peritoneal injection of streptozotocin (STZ), WAF significantly improved fast blood glucose levels, glycosylated hemoglobin levels, body weight loose, blood pressure, and diabetic adverse effects on functions of the kidney and the liver. Taken together, the water extract of Aurantii fructus immaturus may ameliorate diabetes in mice injected with STZ, at least in part, by enhancing insulin secretion and glucose uptake.

지역병원 외래환자의 경구용 당뇨약제의 처방분석

이현태,이경희,박선영,박형건,김라영,권호엽,신억섭 한국병원약사회 2007 병원약사회지 Vol.24 No.1

Diabetes Mellitus is metabolic disease characterized by hyperglycemia resulting from the defective secretion of insulin, or decreased sensitivity of peripheral tissues to insulin, or both. Chronic hyperglycemia, if not well controlled, damages eyes, kidneys, nerves and blood vessels of the humans. The etiology and pathophysiology leading to the hyperglycemia, however, differ from greatly among diabetes patients, suggesting different prevention and treatment strategies might be required. Various classes of antidiabetic agents such as sulfonylureas, meglitinide, biguanide, thiazolidinediones and alpha-glucosidase inhibitors have been developed. However, regional difference in the pattern of administration of those drugs against diabetic patients in Gyeongsang Hospital has been never studied yet. This survey was aimed to investigate the prescription patterns of oral antidiabetic agents based on the same efficacy class of drugs in combination with antihypertensives in the outpatients of Gyeongsang Hospital. The prescriptions of 610 outpatients (M/F 315/295) who were administered oral antidiabetics over 28 days at once from January to February in 2006 were reviewed. We found that mono-therapy including only single efficacy class of antidiabetic drugs was the most prefered one as 45.4%, in which sulfonylureas were the most frequently prescribed drugs as 92.1%, and followed by double-combination therapy using two efficacy classes of drug as 39.5%, in which sulfonylurea with alpha-glucosidase inhibitor combinations were the highest as 43.2% and triple-combination therapy administered three efficacy classes of drug as 14.6%, in which sulfonylurea with biguanide and alpha-glucosidase inhibitor combinations were the highest as 62.9%. We also noticed that about 50.2% (M/F 47%/53%) of outpatients taking antidiabetics were prescribed more than one antihypertensives at the same time. Among them, outpatients who were prescribed only single efficacy class of antihypertensive in combination with antidiabetics were 52.6%, in which the most prefered drug was Calcium channel blocker (CCB) as 39.8%, and then outpatients who were prescribed with two and three classes of antihypertensive drugs were 34.3 % and 12.8 %, respectively. These study results would help not only to understand regional characteristics of diabetic patients and prescription patterns but also to select new antidiabetics or the substitutes in this hospital.

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

Han Ah Lee,Young Chang,Pil Soo Sung,Eileen L. Yoon,Hye Won Lee,Jeong-Ju Yoo,Young-Sun Lee,Jihyun An,Do Seon Song,Young Youn Cho,Seung Up Kim,Yoon Jun Kim 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl- 4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

추출용매 변화에 따른 바나바(Lagerstroemia speciosa Pers.) 잎 추출물의 항당뇨 효과

김균하(Kyun Ha Kim),노상근(Sang Geun Roh),이춘일(Chun-Ri Li),김춘봉(Chun-Feng Jin),김안드레(Andre Kim),최원철(Won Chill Choi) 한국생명과학회 2008 생명과학회지 Vol.18 No.9

본 연구는 바나바 잎 추출 용매에 따른 항당뇨 효과에 관한 것으로 세포 독성 실험을 통하여 인체에 대한 독성이 없음을 확인하였고 β-cell 인슐린 분비 실험을 통하여 항당뇨 효과를 알아보았다. 또한 당뇨 유발쥐를 이용한 인슐린 분비 실험, 체중변화 측정, 혈중 및 혈청의 glucose 농도, 총콜레스테롤 수치, HDL-cholesterol 농도, triglyceride 농도, free fatty acid 농도, langerhans islet에서의 인슐린 분비의 확인을 통해 혈당조절 효과를 비교하였다. 물 혹은 에탄올을 단독으로 이용하여 추출한 추출물이나 70%, 90% 에탄올로 추출한 추출물 보다 열수로 먼저 추출한 후 에탄올로 다시 추출하여 혼합안 추출물이 항당뇨 효과가 더 뛰어남을 알 수 있었다. 이는 친수성(hydrophilic) 유효성분들과 소수성(hydrophobic) 유효성분들의 추출 유무나 함량에 의한 것이다. 특히, 많은 문헌에 언급된 코로소린산이라는 단일 성분(unique)에 의한 항당뇨 효과라기보다는 친수성 및 소수성 폴리페놀 및 항산화성분과 같은 유효성분들이 조합되어(mixture) 항당뇨 효과에 영향을 미치는 것으로 사료된다. This study investigated that the antidiabetic effects of banaba extracts with variety solvents selectivity in vitro and in vivo. Banaba extracts were prepared with water, 70% ethanol, 90% ethanol, 100% ethanol and water-ethanol that of extract twice times sequentially water and ethanol. Cell toxicity and insulin secretion of banaba extracts was tested by MTT (3-[4,5-dimetylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay on hamster insulinoma cell line, HIT-T15. Also we tested that insulin, body weight, blood glucose, total cholesterol, HDL-cholesterol, triglyceride and free fatty acid in streptozotocin diabetic rats. Water-ethanol extract has remarkable antidiabetic effect compare with the other banaba extracts. For water-ethanol extract has both of hydrophilic and hydrophobic antidiabetic materials from banaba. Expecially, corosolic acid, as known as unique polyphenol, has antidiabetic effect studied by many researchers till nowadays. But corosolic acid does not solve in water. Otherwise, we suggest that banaba extract of hydrophilic and hydrophobic materials (polyphenol and antioxidants) mixture more increased antidiabetic effects.

스트렙토조토신으로 유도한 당뇨 마우스에서 번행초 다당 추출물의 항당뇨 효과

최혜정(Hye Jung Choi),이성태(Sung-Tae Yee),주우홍(Woo Hong Joo) 한국생명과학회 2017 생명과학회지 Vol.27 No.5

번행초는 주요 화합물인 수용성 다당류와 cerebroside의 작용에 기인하여 기대되는 항궤양성 약용작물이다. 스트렙토조토신 유도 당뇨마우스에서 번행초의 다당 추출물(TPE)의 항당뇨 효과는 이전에 보고된 바가 없다. 본 연구는 체중 1 kg 당 65 mg의 스트렙토조토신을 복강에 주사하여 확립된 당뇨 마우스에서 TPE의 항당뇨효과를 측정하기 위해 실시하였다. 100 mg 농도의 TPE를 3주간 투여했을 때, 당뇨 마우스의 체중은 유지되었으며, 혈당, 중성지방, 그리고 lactate dehydrogenase, alkaline phosphatase 및 glutamic pyruvic transaminase가 낮은 수준으로 감소함이 관찰되었다. 또한 내당능 실험에서도 TPE의 투여는 대조군인 당뇨 마우스에 비해 혈당수준을 현저하게 감소시켰으며, 실험 가능한 거의 모든 생화학적 요인을 당뇨마우스에 비해 낮은 수준으로 회복시켰다. 따라서 전통적인 약용작물인 번행초의 잠재적인 항당뇨 효능을 본 연구에서 처음으로 증명하였다. Tetragonia tetragonioides seems to be a promising antiulcer medicinal plant due to the presence of water-soluble polysaccharide and cerebroside as its major constituents. There have been no previous studies using T. tetragonioides polysaccharide extract (TPE) to assess its antidiabetic effect in streptozotocin (STZ)-induced diabetes in mice. This study was designed to evaluate the antidiabetic effect of TPE in diabetic mice, which was established by one-week intraperitoneal injection of 65 mg/kg STZ. After three weeks of TPE treatment at a dose of 100 mg/kg, a maintenance of body weight, a decrement in plasma glucose, and low levels of triglyceride, lactate dehydrogenase, alkaline phosphatase, and glutamic pyruvic transaminase were observed in diabetic mice. Furthermore, the ingestion of TPE lowered the blood glucose levels during the oral glucose tolerance test (OGTT) and restored most of the tested parameters to their normal levels. Therefore, the antidiabetic potential of T. tetragonioides has been demonstrated for the first time by our research.

Streptozotocin에 의해 유도된 당뇨쥐에서 연교의 에탄올 추출물의 당뇨 개선 효과

김옥경,Kim, Ok-Kyung 한국응용과학기술학회 2015 한국응용과학기술학회지 Vol.32 No.2

Streptozotocin(STZ)으로 유도된 당뇨 흰쥐에게 연교의 에탄올 추출물을 1일 1회 7일간 1,000mg/kg.b.w의 용량으로 투여 후 glucose함량과 이에 관여하는 효소(glucokinase(GK), glucose-6-phosphatase(G-6-Pase), glucose-6-phosphate dehydrogenase(G-6-PDH)활성과 glycogen 함량, triglyceride(T.G), total cholesterol등의 지질대사에 관여하는 물질들의 함량을 측정한 결과 연교 에탄올 추출물 투여군이 glucose, T.G, total cholesterol 등의 함량과 G-6-Pase 활성이 유의적인 감소를 나타내었으며 glycogen 함량과 GK의 활성이 유의적인 증가를 나타내었다. 이와 같이 연교 에탄올 추출물을 1,000mg/kg.b.w을 당뇨 흰쥐에게 투여한 결과 혈당저하, 지질대사의 개선 효과를 갖는 유효성분을 함유하고 있음을 알 수 있었다. This study was carried to investigate the antidiabetic effect of ethanol extract in Streptozotocin(STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ at a dose of 45mg/kg dissolved in citrate buffer. The ethanol extract of Forsythia Koreana(F.K) was orally administrated once a day for 7 days at a dose of 1,000mg/kg. The contents of serum glucose, triglyceride(TG), total cholesterol were significantly decreased in F.K treated group compared to the those of STZ-control group. The content of hepatic glycogen and activity of glucokinase(GK) were significantly increased, and activity of glucose-6-phoshatase(G-6-Pase) was significantly decreased in F.K treated group compared to the those of STZ-control group, but activity of glucose-6-phosphate dehydrogenase(G-6-PDH) was not significantly increased, These results indicated that ethanol extract of F.K would have antidiabetic effect in STZ-induced diabetic rats.

황기 에탄올 추출물의 항 당뇨 효과

김옥경 한국응용과학기술학회 2019 한국응용과학기술학회지 Vol.36 No.3

This study was carried to investigate the antidiabetic effect of ethanol extract of Astragali Radix(A.R) in Streptozotocin(STZ) induced diabetic rats. Diabetes was induced by intravenous injection of STZ at a dose of 45㎎/㎏ dissolved in citrate buffer. The ethanol extract of A. R was orally administrated once a day for 7 days at a dose of 1,000㎎/㎏. The contents of serum glucose, triglyceride(TG), total cholesterol were significantly decreased in A.R treated group compared to the those of STZ-control group. The content of hepatic glycogen and activities of glucokinase(GK) and glucose-6-phosphate dehydrogenase(G-6-PDH) were significantly increased, and activity of glucose-6-phoshatase(G-6-Pase) was significantly decreased in A.R treated group compared to the those of STZ-control group, These results indicated that ethanol extract of A.R would have antidiabetic effect in STZ-induced diabetic rats. Streptozotocin(STZ)을 45mg/kg.b.w의 용량으로 흰쥐의 미정맥에 투여 한 후 당뇨병이 유발된 당뇨 흰쥐에게 1일 1회 7일간 1,000mg/kg의 용량으로 황기에탄올 추출물을 투여 후 glucose함량과 당대사에 관여하는 효소인 glucose-6-phosphatase(G-6-Pase), glucose-6-phosphate dehydrogenase (G-6-PDH, glucokinase(GK)활성과 glycogen 함량, triglyceride(TG), total cholesterol등의 지질대사에 관여하는 물질들을 측정한 결과 황기 에탄올 추출물 투여군이 glucose, TG, total cholesterol등의 함량과 G-6-Pase 활성의 유의적인 감소를 나타내었으며 glycogen 함량과 G-6-PDH, GK의 활성이 유의적인 증가를 나타내었다. 이와 같이 황기 에탄올 추출물이 항당뇨 개선효과를 갖는 유효성분을 함유하고 있음을 알 수 있었다.

Antidiabetic Activity of Nanopowdered Chitosan in db/db Mice

Mi Hwa Seo,Ju Hyun Park,Hae-Soo Kwak 한국식품과학회 2010 Food Science and Biotechnology Vol.19 No.5

Present study was carried out to examine effects of nanopowdered chitosan on antidiabetic activity in db/db mice. Twenty-eight 8-week-old mice were divided into 4groups: (1) control, nondiabetic control mice; (2) group 1,diabetic control mice with not treated chitosans; (3) group 2, diabetic mice given 2% powdered chitosan; and (4)group 3, diabetic mice given 2% nanopowdered chitosan. The serum glucose in group 3 reduced by 56%, as compared to group 2 (28%). The total serum cholesterol in group 3 decreased by 31.6%, while group 2 reduced by 18.2%. Triglyceride was decreased by 33.6% in group 3and by 22.5% in group 2. The insulin of group 2 and 3 were significantly increased by 51.7 and 92.9%, respectively. Only group 3 was recovered from the β-cell destruction. Based on the result of the study, it is suggested that nanopowdered chitosan has higher antidiabetic activities than powdered.