Natural and semisynthetic protein tyrosine phosphatase 1B (PTP1B) inhibitors as anti-diabetic agents

Wang, Lijun; Jiang, Bo; Wu, Ning; Wang, Shuaiyu; Shi, Dongxia

doi:10.1039/c5ra01754h

Cited by 74 publications

(41 citation statements)

References 94 publications

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“…The extract remarkably inhibited the activity of PTP1B with an IC 50 value in the range of 322-378 µg/mL (Figure 1). This activity is lower than the reported values for a variety of vegetables [22] and seaweed [23].…”

Section: Citationcontrasting

confidence: 48%

Modes of Inhibition of Human Protein-Tyrosine Phosphatase 1B and Aldose Reductase by Moringa oleifera Lam Leaves Extract

Sierra-Campos¹

2017

MOJBOC

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Insulin resistance is the main feature of Type 2 diabetes, due to attenuated or diminished signaling from insulin receptors, resulting in hyperglicemia. Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been suggested as an attractive target to improve insulin sensitivity in different cell types. In addition, hyperglycemia activates the intracellular polyol pathway causing accumulation of sorbitol. This results in cellular water and electrolyte imbalance and oxidative injury. Aldose reductase inhibitors block the rate-limiting enzyme of the polyol pathway, decreasing the accumulation of sorbitol. Moringa oleifera is a plant widely used in traditional Indian and African medicine, e.g. for its antidiabetic effect. However, studies about the inhibitory effect of M. oleifera on diabetic complications mediated via diverse enzymes as PTP1B and aldose reductase have not been carried out yet. To potentially identify targets responsible for this antidiabetic effect, we conducted kinetic studies to investigate the inhibitory capacity of M. oleifera extract (MOE) over PTP1B. MOE possess the highest inhibitory activity against PTP1B (IC 50 value of 346.8 µg/mL). We also found that the extract inhibited the recombinant human aldose reductase (rhAR) activity with an IC 50 of 3.55 µg/mL. Subsequent kinetic analysis revealed that MOE behaved as an uncompetitive inhibitor (K i of 19.65 µg/mL) against PTP1B, since it markedly modified K m and also modified V max to a lesser extent. As for the rhAR, the extract behaved as mixed inhibitor (Ki = 18.6 µg/mL, alpha = 1.3). Our results help to understand the inhibition mechanism of PTP1B and rhAR by phenolic compounds and flavonoids present in MOE, which is essential for the development of improved natural inhibitors.

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Section: Citationcontrasting

confidence: 48%

Modes of Inhibition of Human Protein-Tyrosine Phosphatase 1B and Aldose Reductase by Moringa oleifera Lam Leaves Extract

Sierra-Campos¹

2017

MOJBOC

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“…Diabetes mellitus is a chronic disease that is triggered by insulin resistance or deficiency. This disease is one of the major risks to human well-being worldwide [105]. Long-term use of oral hypoglycaemic agents may reduce their pharmacological activity.…”

Section: Anti-diabetesmentioning

confidence: 99%

Ursolic Acid and Its Derivatives as Bioactive Agents

et al. 2019

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Non-communicable diseases (NCDs) such as cancer, diabetes, and chronic respiratory and cardiovascular diseases continue to be threatening and deadly to human kind. Resistance to and side effects of known drugs for treatment further increase the threat, while at the same time leaving scientists to search for alternative sources from nature, especially from plants. Pentacyclic triterpenoids (PT) from medicinal plants have been identified as one class of secondary metabolites that could play a critical role in the treatment and management of several NCDs. One of such PT is ursolic acid (UA, 3 β-hydroxy-urs-12-en-28-oic acid), which possesses important biological effects, including anti-inflammatory, anticancer, antidiabetic, antioxidant and antibacterial effects, but its bioavailability and solubility limits its clinical application. Mimusops caffra, Ilex paraguarieni, and Glechoma hederacea, have been reported as major sources of UA. The chemistry of UA has been studied extensively based on the literature, with modifications mostly having been made at positions C-3 (hydroxyl), C12-C13 (double bonds) and C-28 (carboxylic acid), leading to several UA derivatives (esters, amides, oxadiazole quinolone, etc.) with enhanced potency, bioavailability and water solubility. This article comprehensively reviews the information that has become available over the last decade with respect to the sources, chemistry, biological potency and clinical trials of UA and its derivatives as potential therapeutic agents, with a focus on addressing NCDs.

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“…Diabetes mellitus (DM) a chronic metabolic disorder has become one of the world's most serious health concerns. Clinically, there are four types of DM, and type 2 diabetes mellitus (T2DM) is the most common form that causes many severe secondary complications, such as atherosclerosis, renal dysfunction and failure, cardiac abnormalities and ocular disorders (Rengasamy et al 2013;Wang et al 2015;Guo et al 2015). Shin's study showed that CGA (1) (10 and 20 mg kg -1 , intraperitoneal injection) effectively preserved the expression of tight junction protein and attenuated STZ-induced diabetic retinopathy in mice (Shin et al 2013).…”

Section: Hypoglycemic Activitymentioning

confidence: 99%

Lonicerae japonicae flos and Lonicerae flos: a systematic review of ethnopharmacology, phytochemistry and pharmacology

et al. 2019

Phytochem Rev

113

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Lonicerae japonicae flos (called Jinyinhua, JYH in Chinese), flowers or flower buds of Lonicera japonica Thunberg, is an extremely used traditional edible-medicinal herb. Pharmacological studies have already proved JYH ideal clinical therapeutic effects on inflammation and infectious diseases and prominent effects on multiple targets in vitro and in vivo, such as pro-inflammatory protein inducible nitric oxide synthase, toll-like receptor 4, interleukin-1 receptor. JYH and Lonicerae flos [called Shanyinhua, SYH in Chinese, flowers or flower buds of Lonicera hypoglauca Miquel, Lonicera confusa De Candolle or Lonicera macrantha (D.Don) Spreng]which belongs to the same family of JYH were once recorded as same herb in multiple versions of Chinese Pharmacopoeia (ChP). However, they were listed as two different herbs in 2005 Edition ChP, leading to endless controversy since they have close proximity on plant species, appearances and functions, together with traditional applications. In the past decades, there has no literature regarding to systematical comparison on the similarity concerning research achievements of the two herbs. This review comprehensively presents similarities and differences between JYH and SYH retrospectively, particularly proposing them the marked differences in botanies, phytochemistry and pharmacological activities which can be used as evidence of separate list of JYH and SYH. Furthermore, deficiencies on present studies have also been discussed so as to further research could use for reference.

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Natural and semisynthetic protein tyrosine phosphatase 1B (PTP1B) inhibitors as anti-diabetic agents

Cited by 74 publications

References 94 publications

Modes of Inhibition of Human Protein-Tyrosine Phosphatase 1B and Aldose Reductase by Moringa oleifera Lam Leaves Extract

Modes of Inhibition of Human Protein-Tyrosine Phosphatase 1B and Aldose Reductase by Moringa oleifera Lam Leaves Extract

Ursolic Acid and Its Derivatives as Bioactive Agents

Lonicerae japonicae flos and Lonicerae flos: a systematic review of ethnopharmacology, phytochemistry and pharmacology

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