Effects of keishi-ka-jutsubu-to (traditional herbal medicine: Gui-zhi-jia-shu-fu-tang) on in vivo insulin action in streptozotocin-induced diabetic rats

In vivo insulin resistance is a characteristic of the liver and peripheral tissues in 10-wk-old female rats with non-insulin-dependent diabetes induced by streptozotocin given on day 5 after birth. Oral administration of vanadate (0.2 mg/ml) for 20 days in the diabetic rats lowered their plasma glucose levels to normal values without affecting their basal plasma insulin levels. In the basal state as well as after submaximal or maximal hyperinsulinemia (euglycemic clamp studies), peripheral glucose utilization and hepatic glucose production in vivo were normalized in the diabetic rats after the vanadate treatment. In wheat germ agglutinin purified receptors, 125I-labeled porcine insulin binding, basal and insulin-stimulated insulin receptor kinase activities for both the autophosphorylation of the beta-subunit and the phosphorylation of the artificial substrate poly (Glu-Tyr) 4:1, were found identical in diabetic and control rats, treated or not with vanadate. Liver phosphoenolpyruvate carboxykinase activity was significantly enhanced in untreated diabetic rats (P less than 0.01) as compared with control rats and returned to normal values after the 20-day vanadate treatment. Thus, in that model of non-insulin-dependent diabetes, 1) oral vanadate exerts a corrective insulin-like effect on impaired insulin action both at the level of liver and peripheral tissues, 2) impaired insulin action with no alteration of the insulin receptor tyrosine kinase is observed in the liver of untreated rats, and 3) corrective effect of vanadate on liver glucose metabolism is probably distal to the insulin receptor kinase activity.

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Sepsis-induced changes in in vivo insulin action in diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.3.e301 ◽

1989 ◽

Vol 257 (3) ◽

pp. E301-E308 ◽

Cited By ~ 2

Author(s):

C. H. Lang ◽

C. Dobrescu

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Insulin Action ◽

Plasma Concentrations ◽

Diabetic Rats ◽

Hepatic Insulin Resistance ◽

Blood Levels ◽

Euglycemic Hyperinsulinemic Clamp ◽

Glucose Output

The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance. Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined with the use of [3-3H]glucose initiated 18 h after the first injection of bacteria. Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique. Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals. Diabetes alone decreased both insulin sensitivity and responsiveness. When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity. Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals. Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals. These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines.

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The Optimization Method for Synthesis of 99mTc-Rutin as Potential Radiotracer in The Development of Cancer Drugs From Flavonoid

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev10iss2pp80-87 ◽

2019 ◽

Vol 10 (2) ◽

pp. 80

Author(s):

Eva Maria Widyasari ◽

Esty Kusumawardhany ◽

Rizky Juwita Sugiharti ◽

Maula Eka Sriyani ◽

Muharam Marzuki

Keyword(s):

Herbal Medicine ◽

Cancer Treatment ◽

Antioxidant Activities ◽

Scientific Information ◽

Radiochemical Yield ◽

Optimization Method ◽

Biological Information ◽

Cancer Drugs ◽

Traditional Herbal Medicine

Based on the Basic Health Research Data of Ministry of Health's of Indonesia in 2013, mortality rates from malignant and tumor malignancies in Indonesia are still high with prevalence of cancer is about 1.4%. Chemotherapy is still the primary choice in cancer modality that uses chemotherapeutic drugs to eradicate and inhibit the growth of cancer cells; however the cost this treatment is extremely high. Therefore, patient tends to seek alternative treatment such as consuming traditional herbal medicine for cancer treatment. Rutin is one of the attractive phytochemicals flavonoids because of its antioxidant activities. However, as traditional herbal medicine, its effectiveness is not yet been fully established due to the lack of scientific information. A radiotracer can be defined as a specific radiolabeled molecule that monitors the in vivo behaviour of a functional molecule, and can be used to provide biological information in a living system. Hence, to provide pharmacological information of rutin for cancer treatment, we synthesized radiolabeled flavonoid 99mTc-rutin as radiotracer. The aim of the present study is to develop 99mTc-rutin under varying conditions of rutin quantity, reducing agent concentration and incubation time. Labeling studies were performed by changing the selected parameters one by one and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency, 99mTc-rutin was obtained with preparation of 700 μg of rutin with addition of 20 μg of SnCl2.2H2O as reductor and 1-3 mCi 99mTcO4- without any incubation. Radiochemical yield of 99mTc-rutin was determined with radio thin layer chromatography which was found 99.28 ± 0.14% and stable up to 4 hour. From the result of this study, the successfully labeled 99mTc-rutin can be used as a reference for following preclinical study. Furthermore radiolabeled 99mTc-rutin is expected as tools in research and development of rutin as cancer drugs from natural product to obtain detailed information its efficacy.Keywords: radiotracer, 99mTc-rutin, cancer, labeled compounds

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Active Components from Traditional Herbal Medicine for the Potential Therapeutics of Idiopathic Pulmonary Fibrosis: A Systemic Review

The American Journal of Chinese Medicine ◽

10.1142/s0192415x2150052x ◽

2021 ◽

pp. 1-22

Author(s):

Ebuka-Olisaemeka Nwafor ◽

Peng Lu ◽

Yiting Liu ◽

Hui Peng ◽

Huan Qin ◽

...

Keyword(s):

Herbal Medicine ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Adverse Reactions ◽

Analytical Data ◽

Systemic Review ◽

Active Components ◽

Traditional Herbal Medicine ◽

Potential Therapeutics

Idiopathic pulmonary fibrosis (IPF), a tumor-like disease, is a serious and fatal pulmonary inflammatory condition usually characterized by irreversible destruction of the lung parenchyma, excessive matrix accumulation, and decline in lung function. IPF still remains a great burden to the universe. At the moment, the available therapeutic regimens utilized for IPF such as non-pharmacological therapies (lung transplantation) and pharmacological therapies (drugs, nintedanib, pirfenidone, etc.) are normally accompanied by significant limitations, such as adverse reactions, low bioavailability, poor selectivity, low-tissue distribution, in vivo instability, systemic toxicity, inconveniency and unsafe usage. There is a need for the exploration and discovery of new novel remedies by researchers and scientists globally. Recent numerous preliminary studies have laid significant emphasis and demonstrated the antifibrotic importance, good curative actions (little or no adverse reactions), and multiple target sites of the active components from traditional herbal medicine (THM) against IPF, which could serve as a modern, alternative and potential therapeutics or drug candidates in treating IPF. This paper extensively summarizes the pharmacological actions and signaling pathways or mechanisms of active components obtained from THM for treating IPF. Moreover, the sources and modernization, markets, relevant FDA and CFDA studies (the USA and China), preclinical analysis, and various compositions of THM currently under clinical trials are also highlighted. Additionally, this present analytical data would be instrumental towards further drug progression or advancement of active components from THM for the potential therapeutics of IPF in the future.

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Antibacterial and Toxicity Activities of Indonesian Herbal Medicine Extracts Used for Postpartum Treatment

HAYATI Journal of Biosciences ◽

10.4308/hjb.28.3.232 ◽

2021 ◽

Vol 28 (3) ◽

pp. 232

Author(s):

Wiwit Denny Fitriana ◽

Sri Banun Titi Istiqomah ◽

Devi Anggraini Putri ◽

Taslim Ersam ◽

Adi Setyo Purnomo Purnomo ◽

...

Keyword(s):

Herbal Medicine ◽

Staphylococcus Epidermidis ◽

Pathogenic Bacteria ◽

Scientific Evidence ◽

Rhodopseudomonas Palustris ◽

Positive Control ◽

Traditional Herbal Medicine ◽

Ic50 Values ◽

Ld50 Value

Postpartum treatments have been used by local women in Indonesia for some time now. One commonly used postpartum treatment is the consumption of a traditional herbal medicine called PHM-1 during the first 40 days after childbirth. In addition, a second medicine known as PHM-2 is taken for days 41-80. However, sufficient scientific evidence about the benefits of this postpartum herbal medicine does not exist. In this study, the antibacterial abilities of PHM-1 and PHM-2 therefore was evaluated and showed positive potential for both. Low IC50 values were obtained against pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Rhodopseudomonas palustris, Ralstonia pickettii, and Staphylococcus epidermidis and compared with chloramphenicol as a positive control. The antibacterial activity of both PHM-1 and PHM-2 against R. pickettii had the highest inhibitory activity as evidenced by the lowest IC50 values of 11.16 and 6.26 μg/ml, respectively. Furthermore, an in vivo acute toxicity test showed that PHM-1 produced a low LD50 value of 3.28 g/kg BW for both of male and female mice. These results support the use of both PHM-1 and PHM-2 as antibacterial treatments for postpartum women.

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