EditorialDiabetes and Metabolism Disorders Medicinal Plants:A Glance at the Past and a Look to the Future 2018

Hilal Zaid ,1,2 Akhilesh K. Tamrakar ,3 Mohammed S. Razzaque,3,4 and Thomas Efferth5

1Qasemi Research Center, Al-Qasemi Academy, P.O. Box 124, Baqa-El-Gharbia 30100, Israel2Faculty of Sciences, Arab American University, P.O. Box 240, Jenin, State of Palestine3CSIR-Central Drug Research Institute, Lucknow 226031, India4Department of Pathology, Lake Erie College of Osteopathic Medicine, Erie, Pennsylvania, USA5Johannes Gutenberg University, Mainz, Germany

Correspondence should be addressed to Hilal Zaid; hilal.zaid@gmail.com

Received 26 September 2018; Accepted 26 September 2018; Published 30 September 2018

Copyright © 2018 Hilal Zaid et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Diabetes is one of the world’s most widespread diseases,characterized by persistent hyperglycemia and related tometabolic disorder, affecting over 327 million people andcausing about 300,000 deaths annually [1]. Despite greatadvances in prevention and therapy, existing treatmentsfor this disorder have serious side effects. On the otherhand, in the modern and contemporary world, the incidenceof metabolic disorders and diabetes is rising continuouslydue to modernization in life style and unhealthy dietaryhabits, imposing an urgent need for new therapies for themanagement of this deadly disease. Plants used in traditionalmedicine represent a valuable source in the search for newmedicinal compounds. In traditional system of medicine,at least 1200 species of medicinal plants are used for theirantidiabetic attributes. However, only a small proportion ofsuch plants have been scientifically validated [2].

Currently, we are witnessing a great progress in evidence-based modern medicine and pharmacology. The character-ization of pharmacological and biological effects of herbal-based medicines is becoming more competitive and com-plex, with the involvement of experts in this research areabelonging to different scientific fields, including botany,chemistry, biochemistry, immunology, molecular biology,and bioinformatics. However, despite this great progress inevidence-based modern medicine and pharmacology, tra-ditional medicinal plants continue to be practiced withoutregulations in many countries [3]. It is crucial hence tokeep on studying medicinal plants efficacy including theirtoxicity in order to prevent their abuse. This special issue

provides a comprehensive overview on physiological as wellasmolecular and biochemical efficacy ofmedicinal plants andnatural active compounds in treatingmetabolic disorders anddiabetes. For this special issue, the editorial office received23 papers, and after rigorous peer review process 12 paperswere accepted for publication. All published articles focusedon the theme of this special issue, dealing with biochemicalefficacy, molecular mechanism, or clinical efficacy of plant-derived samples for themanagement of diabetes or associatedmetabolic disorders.

C. Rugerio-Escalona et al. evaluated the antihyper-glycemic potential of the crude and fractional methanolicextracts of Hamelia patens Jacq in streptozotocin-inducedhyperglycemic rats. They reported that repeated administra-tions of the crude or fractional methanolic extract for 20days lowered blood glucose to a normal level. The extractswere also shown to have significant 𝛼-glucosidase inhibitoryactivity and protective effects of kidney and liver functionparameters. They further subjected the plant extract forquantitative phytochemical and chromatographic analysisand identified five compounds. Out of those, epicatechin andchlorogenic acid had demonstrated antihyperglycemic effect.Considering its antihyperglycemic potential, the authorsproposed the extracts ofHamelia patens as efficacious sourcefor the treatment of diabetes.

Increased incidences of diabetes are closely associatedwith increase in obesity and related hyperlipidemia. Cur-rently available synthetic drugs to lower weight or serum lipidin obese patients have been associated with adverse effect

HindawiEvidence-Based Complementary and Alternative MedicineVolume 2018, Article ID 5843298, 3 pageshttps://doi.org/10.1155/2018/5843298

2 Evidence-Based Complementary and Alternative Medicine

progression of drug resistance. Therefore a well-designedclinical trial to establish the efficacy of an intended moleculeis very important. In the clinical study by S. Kang et al.,the authors evaluated the impact of Citrus unshiu peelpellet (CUPP) on obesity and lipid profile. They selected 118patients, including 88 females with bodymass index > 23 andgave them Citrus unshiu peel pellet for 4 weeks and observeda significant decrease in BMI in all subjects after CUPPtreatment. They also observed a significant decrease in totalcholesterol and triglycerides levels. The authors concludedthat CUPP could aid in weight control and improve totalcholesterol level, and they proposed a large-scale trial toestablish the clinical benefits of CUPP.

In another pilot study performed by P. Algenstaedt et al.,the authors test the effect of daily consumption of Morindacitrifolia (Noni) fruit juice on the physiological status of type2 diabetic patients. They treated twenty patients with type2 diabetes with Morinda citrifolia fruit juice for eight weekswith regular monitoring of blood glucose levels and otherbiochemical parameters. They observed that Morinda citri-folia fruit juice consumption decreased fasting blood glucoselevel in diabetic patients but it did not cause hypoglycemiain normoglycemic patients. They also reported decrease inmean HbA1c and CRP values and improvement in insulinexcretion and blood cholesterol status in Morinda citrifoliafruit juice treated patients. The authors proposed Morindacitrifolia fruit juice as a suitable additive to the diet of diabeticpatients.

Enhanced rate of morbidity andmortality of diabetics hasbecome a global health problem and puts a huge economicburden on the world population, urging researchers to clarifythe pathogenesis of diabetes using advanced techniques.Proteomic technologies are large-scale research tools thatcan provide abundant data regarding the pattern of proteinexpression and are widely used to explore the molecularmechanisms underlying the function of complex bioactivemixtures. X. Qiu and colleagues reported a comparative pro-teomic analysis of two differently extracted Coptis Chinensis(CC) in the treatment of type 2 diabetes. They establisheda rat model of type 2 diabetes, treated it with supercritical-extracted CC and gastric juice extracted CC, and comparedvarious phenotypic and biochemical parameters betweenthe groups. The report showed a significant decrease intriglyceride, total cholesterol, and low density lipoproteinin both CC-treated groups. Additionally, they reported 15proteins to be differentially regulated in both CC-treatedgroups. These proteins were found to be associated withglucosemetabolism, insulin action, immunity, inflammation,lipidmetabolism, oxidation, and antioxidation. From the dataauthors established that the two differently extracted CC didnot show significant differences in terms of their treatmentefficacy.

Type 2 diabetes is characterized by insulin resistance inperipheral tissues, including skeletal muscle, liver, and adi-pose. Skeletal muscle is the major site for glucose utilizationand insulin resistance in skeletal muscle is characterizedby impaired translocation of insulin sensitive glucose trans-porter, GLUT4, to cell surface causing decreased rate of glu-cose uptake. Therefore, interventions with ability to increase

GLUT4 translocation to cell surface can be beneficial for themanagement of insulin resistance. In the in vitro study by S.Kadan et al., the authors assessed the chemical composition,cytotoxicity, and antidiabetic activity of Gundelia tournefortiiextracts. They revealed 39 compounds in the extracts andfound both the methanol and hexane extract to be safe up to250𝜇g/ml in vitro. Effect of extracts on glucose metabolismwas assessed by measuring GLUT4 translocation in musclecells, and it was found that methanol extract is more efficientin GLUT4 translocation enhancement. The authors proposedthat Gundelia tournefortii exerts antidiabetic activity byenhancing GLUT4 translocation to the cell surface in skeletalmuscle.

Inhibition of 𝛼-glucosidase and 𝛼-amylase, which digestdietary starch into glucose, has been an established methodfor controling blood sugar levels. However, currently avail-able drugs under this category have been reported withunpleasant gastrointestinal side effects that frequently resultin therapy abandonment. Therefore, it is necessary to con-tinue the search for new alternatives to 𝛼–glucosidase andpancreatic lipase inhibitors, with milder side effects andwhich contribute to the treatment of obesity and type 2diabetes mellitus, in conjunction with current therapies.With the aim of identifying new pancreatic lipase and𝛼–glucosidase inhibitors for the management of diabetes, D.Morales et al. reported potential inhibitor for these enzymesfrom the hydroalcoholic extract of Ludwigia octovalvis. Theauthors reported identifying and characterizing one flavone(isoorientin) with considerable inhibitory effect of pancreaticlipase and two compounds with potential inhibitory effectagainst 𝛼–glucosidases (ethyl gallate and gallic acid). Thesefindings might be useful in the development of a potentialnovel phytomedicine.

In a similar study, R. S. Shenoy et al. investigated thetriterpene glycoside (TG) fraction, isolated from the etha-nolic extract of Gymnema sylvestre, for inhibitory activityagainst different glucosidases. TG was characterized by beinga mixture of triterpene glycosides, gymnemic acid I, IV, VII,and gymnemagenin and exhibited effective inhibition of yeast𝛼- glucosidase, sucrase, maltase, and pancreatic 𝛼-amylase.TG did not exhibit any toxic effects on 𝛽-cell viability,showed protection against H2O2 induced ROS generation,and stimulated glucose-induced insulin secretion in 𝛽-cells.The authors proposed TG as a functional food ingredient anda safe nutraceutical candidate for management of diabetes.

Metabolomics is used to evaluate the characteristicsand interactions of low molecular weight metabolites undera specific set of conditions. It is a powerful analyticalstrategy to identify the metabolites in vivo and clarifymetabolic pathways. Especially for metabolic disease, such asT2DM, metabolomics offers an opportunity to test multiplemetabolic markers in large settings. J. Liu et al. reported ametabolomics-based clinical efficacy of Tangzhiqing tablet(TZQ), a Chinese patent medicine, consisting of five herbs,Paeonia lactiflora,Morus alba, Nelumbonucifera, Salviamilti-orrhiza, andCrataegus pinnatifida, for type 2 diabetesmellituswith hypertriglyceridemia. In clinical study with type 2diabetic patients, they observed that TZQ could reduce gly-cosylated hemoglobin (HbA1c) and fasting insulin, correlated

Evidence-Based Complementary and Alternative Medicine 3

with the baseline level of triglyceride. In metabolomics datathey observed a significant difference between patients andhealthy volunteers and identified 17 biomarkers. After 12-week treatment with TZQ they found significant decreasein 11 biomarkers and suggested that TZQ could improve themetabolomic abnormalities in the participants.

Obesity is the major risk factor for increasing incidencesof diabetes. Therefore, search towards a molecule that canmitigate both hyperglycemia and obesity is of higher pri-ority for the management of metabolic syndrome. R. O.Malematja et al. evaluated the acetone leaf extract of Sennaitalic for its cytotoxic, antiglycation, and lipolytic effect.They also evaluated its effect on glucose uptake and GLUT4translocation to cell surface and adipogenesis in 3T3-L1adipocytes. They found that extract had no adverse effect oncell viability. It showed significant antiglycation effect anddecreased the expression of various adipokines. They alsoobserved increased rate of glucose uptake associated withenhanced GLUT4 translocation and expression upon extracttreatment in combination with insulin, mediated throughthe PI3K-dependent pathway. In independent study by J. Leeet al., authors investigated the synergistic effect of BupleuriRadix and Scutellariae Radix, an herbal combination fromKorean medicine on obesity model of 3T3-L1 adipocytes.They reported that combination significantly decreased lipidaccumulation and expression of the important adipogenicfactor PPAR𝛾 and C/EBP𝛼 and their downstream genesin 3T3-L1 adipocytes. Furthermore, the combination wasreported to activate AMP-activated protein kinase alpha,thereby regulating energy metabolism.

In the study by C. Tian et al., the authors investigatedthe effect and mechanism of action of Wushenziye formula,a traditional Chinese medicine, on skeletal muscle insulinresistance in type 2 diabetes. They observed significantimprovement in fasting blood glucose, glycosylated serumproteins, glycosylated hemoglobin, insulin, and insulin resis-tance index in type 2 diabetic Goto-Kakizaki rats. Underin vitro condition, they observed increased glucose con-sumption, upregulated expression of IRS-1, Akt, and GLUT4,and decreased expression of PTP1B in skeletal muscle cellstreated with Wushenziye formula. The author demonstratedthat Wushenziye formula regulated glucose metabolismthrough modulating PTP1B/ IRS-1/AKT/GLUT4 signalingand offered Wushenziye formula as a potential candidate forthe management of type 2 diabetes.

The study by Q. Liang et al. aimed to understand themolecular mechanisms of Zuo Gui Wan (ZGW), classicformula in traditional Chinesemedicine, on impaired glucosetolerance in mouse embryo. They used high glucose loadedtwo-cell stage mouse embryos as a model and utilized single-cell RNA sequencing technology for transcriptome analysis.They observed that ZGW reversed high glucose-mediateddownregulation of genes in the ribosome pathway, leadingto prevention of high glucose-mediated embryo cell death.They also observed that ZGW promoted sugar metabolismvia tricarboxylic acid cycle through upregulating the genesin the respiratory chain and oxidative phosphorylation. Thestudy revealed the global gene regulation changes of highglucose affecting two-cell stage embryos and also provided

insight into the potential molecular mechanisms of ZGW onthe IGT.

Overall, in light of this special issue, plant based therapeu-tics can be a better option for themanagement of diabetes andrelated metabolic complications. However, proper scientificvalidation of efficacy in established experimental models,clinical efficacy, and assessment for the adverse side effectsis of utmost important, for their further development.

Conflicts of Interest

The editors declare that they have no conflicts of interestregarding the publication of this special issue.

Acknowledgments

We are thankful to all contributors of this special issuefor their valuable research papers. We are grateful to thereviewers for their constructive criticism and timely responsethat made this special issue possible. Our sincere thanks andgratitude go to the editorial board of eCAM for inviting us toedit this special issue. The editorial board hopes that readerswill enjoy this special issue.

Hilal ZaidAkhilesh K. Tamrakar

Mohammed S. Razzaque�omas Efferth

References

[1] H. Zaid, B. Saad, A. A.Mahdi,A. K. Tamrakar, P. S. Haddad, andF.U.Afifi, “Medicinal Plants andNatural Active Compounds forDiabetes and/or Obesity Treatment,” Evidence-Based Comple-mentary and Alternative Medicine, vol. 2015, Article ID 469762,2 pages, 2015.

[2] B. Saad, H. Zaid, S. Kadan, and S. Shanak, Anti-diabetes andAnti-obesity Medicinal Plants and Phytochemicals: Safety, Effi-cacy, and ActionMechanisms, Springer International PublishingAG, 2017.

[3] H. Zaid, A. A. Mahdi, A. K. Tamrakar, B. Saad, M. S. Razzaque,and A. Dasgupta, “Natural active ingredients for diabetes andmetabolism disorders treatment,” Evidence-Based Complemen-tary and Alternative Medicine, vol. 2016, Article ID 2965214, 2pages, 2016.

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