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10 pages, 1795 KiB

Open AccessCommunication

Identification of Renoprotective Phytosterols from Mulberry (Morus alba) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells

by Dahae Lee, Seoung Rak Lee, Bang Ju Park, Ji Hoon Song, Jung Kyu Kim, Yuri Ko, Ki Sung Kang and Ki Hyun Kim

Plants 2021, 10(11), 2481; https://doi.org/10.3390/plants10112481 - 17 Nov 2021

Cited by 1 | Viewed by 1907

Abstract

The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (Morus alba L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. Morus alba fruit is a well-known edible fruit commonly [...] Read more.

The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (Morus alba L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. Morus alba fruit is a well-known edible fruit commonly used in traditional folk medicine. Chemical investigation of M. alba fruit resulted in the isolation and identification of six phytosterols (1–6). Their structures were determined as 7-ketositosterol (1), stigmast-4-en-3β-ol-6-one (2), (3β,6α)-stigmast-4-ene-3,6-diol (3), stigmast-4-ene-3β,6β-diol (4), 7β-hydroxysitosterol 3-O-β-d-glucoside (5), and 7α-hydroxysitosterol 3-O-β-d-glucoside (6) by analyzing their physical and spectroscopic data as well as liquid chromatography/mass spectrometry data. All compounds displayed protective effects against cisplatin-induced LLC-PK1 cell damage, improving cisplatin-induced cytotoxicity to more than 80% of the control value. Compound 1 displayed the best effect at a relatively low concentration by inhibiting the percentage of apoptotic cells following cisplatin treatment. Its molecular mechanisms were identified using Western blot assays. Treatment of LLC-PK1 cells with compound 1 decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound 1 significantly suppressed cleaved caspase-3 in cisplatin-induced LLC-PK1 cells. Taken together, these findings indicated that cisplatin-induced apoptosis was significantly inhibited by compound 1 in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol (1) as an adjuvant candidate for treating cisplatin-induced nephrotoxicity. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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10 pages, 1663 KiB

Open AccessCommunication

Phytochemical Investigation of Bioactive Compounds from White Kidney Beans (Fruits of Phaseolus multiflorus var. Albus): Identification of Denatonium with Osteogenesis-Inducing Effect

by Yong Hoon Lee, Joo-Hyun Hong, Kun Hee Park, Seon-Hee Kim, Jin-Chul Kim, Do Hoon Kim, Yu Hwa Park, Kye Wan Lee, Jung Kyu Kim and Ki Hyun Kim

Plants 2021, 10(10), 2205; https://doi.org/10.3390/plants10102205 - 17 Oct 2021

Cited by 1 | Viewed by 2224

Abstract

Phaseolus multiflorus var. albus (Leguminosae), commonly known as “white kidney bean”, is a twining perennial vine whose fruit has been used as a popular food worldwide owing to its high nutritional content, in terms of proteins, carbohydrates, fats, and vitamins. As part of [...] Read more.

Phaseolus multiflorus var. albus (Leguminosae), commonly known as “white kidney bean”, is a twining perennial vine whose fruit has been used as a popular food worldwide owing to its high nutritional content, in terms of proteins, carbohydrates, fats, and vitamins. As part of our ongoing study to investigate novel bioactive components from various natural resources, a phytochemical investigation of the extract of P. multiflorus var. albus fruits resulted in the isolation of three phenolic compounds (1–3) and one dipeptide (4). The chemical structures of the compounds (1–4) were determined through 1D and 2D nuclear magnetic resonance spectroscopy and high-resolution-liquid chromatography–mass spectrometry; they were identified as denatonium (1), trans-ferulic acid ethyl ester (2), eugenin (3), and α-L-glutamyl-L-Leucine (4). Intriguingly, denatonium (1) is known to be the most bitter chemical compound. To the best of our knowledge, denatonium (1) was identified from natural sources for the first time, and compounds 2–4 were reported for the first time from P. multiflorus var. albus in this study; however, compound 2 turned out to be an artifact produced by an extraction with ethanol. The isolated compounds 1–4 were tested for their regulatory effects on the differentiation between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs). Compound 4 slightly suppressed the adipogenic differentiation of MSCs, and compounds 1 and 4 stimulated osteogenic differentiation, unlike the negative control. These findings provide experimental evidence that compounds 1 and 4 may induce the osteogenesis of MSCs and activate bone formation. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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9 pages, 1808 KiB

Open AccessArticle

Unusual Bicyclo[3.2.1]Octanoid Neolignans from Leaves of Piper crocatum and Their Effect on Pyruvate Dehydrogenase Activity

by Yu Juan Chai, Younghoon Go, Hai Qi Zhou, Hong Xu Li, Sun Joo Lee, Yeo Jin Park, Wahyu Widowatib, Rizal Rizal, Young Ho Kim, Seo Young Yang and Wei Li

Plants 2021, 10(9), 1855; https://doi.org/10.3390/plants10091855 - 07 Sep 2021

Cited by 5 | Viewed by 1920

Abstract

Three undescribed bicyclo[3.2.1]octanoid neolignan glucosides, along with a known neolignan, were isolated from the leaves of Piper crocatum Ruiz & Pav. Their chemical structures were elucidated using extensive spectroscopic analyses including 1D and 2D NMR experiments and HR-ESI-MS analysis, as well as through [...] Read more.

Three undescribed bicyclo[3.2.1]octanoid neolignan glucosides, along with a known neolignan, were isolated from the leaves of Piper crocatum Ruiz & Pav. Their chemical structures were elucidated using extensive spectroscopic analyses including 1D and 2D NMR experiments and HR-ESI-MS analysis, as well as through comparison with previously reported data. Two compounds were assessed for their inhibitory effect against pyruvate dehydrogenase E1α S300 phosphorylation. The fluorescent image suggested that both compounds (60 µM) revealed a stronger inhibition effect than the positive control (dichloroacetate, DCA 5 mM), with IC₅₀ values of 99.82 µM and 80.25 µM, respectively. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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12 pages, 2756 KiB

Open AccessArticle

The Protective Effect of Adenocaulon himalaicum Edgew. and Its Bioactive Compound Neochlorogenic Acid against UVB-Induced Skin Damage in Human Dermal Fibroblasts and Epidermal Keratinocytes

by Hye Shin Ahn, Hyun Jae Kim, Changseon Na, Dae Sik Jang, Yu-Kyong Shin and Sun Hee Lee

Plants 2021, 10(8), 1669; https://doi.org/10.3390/plants10081669 - 13 Aug 2021

Cited by 11 | Viewed by 2990

Abstract

Skin aging induced by ultraviolet (UV) irradiation increases expression of matrix metalloproteinase-1 (MMP-1) and destroys collagen fibers, as a result accelerating wrinkle formation. Natural products have been received scientific attention as utilized agents against photoaging. The aim of this study was to investigate [...] Read more.

Skin aging induced by ultraviolet (UV) irradiation increases expression of matrix metalloproteinase-1 (MMP-1) and destroys collagen fibers, as a result accelerating wrinkle formation. Natural products have been received scientific attention as utilized agents against photoaging. The aim of this study was to investigate the protective effect of Adenocaulon himalaicum Edgew. extract (AHE) against ultraviolet B (UVB)-induced skin damage, and to explain the underlying mechanisms in human dermal fibroblasts and epidermal keratinocytes. AHE effectively protects skin photoaging by preventing collagen degradation through MMP-1 inhibition via the MAPK/AP-1 signaling pathway. AHE significantly increased the expression of skin hydration factors, such as filaggrin, involucrin, loricrin, and caspase-14. To find how AHE possesses a direct impact on cellular activities, we identified neochlorogenic acid as a bioactive component of AHE for the first time. Neochlorogenic acid showed the anti-photoaging effect through ameliorating UVB-induced collagen degradation, reinforcing the skin barrier. Like the AHE-regulating mechanism, neochlorogenic acid modulates the MAPK/AP-1 signaling pathway and skin hydration factors. Taken together, these results suggest that AHE and neochlorogenic acid are well-qualified candidate for enhancing the conditions of photoaged skin. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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19 pages, 3301 KiB

Open AccessArticle

Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of Acacia arabica Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents

by Prawej Ansari, Peter R. Flatt, Patrick Harriott, J. M. A. Hannan and Yasser H. A. Abdel-Wahab

Plants 2021, 10(6), 1190; https://doi.org/10.3390/plants10061190 - 11 Jun 2021

Cited by 11 | Viewed by 3423

Abstract

Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and [...] Read more.

Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes, and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation, and phytoconstituents were isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of A. arabica (HWAA) increased insulin release from clonal β cells and mouse islets by 1.3–6.8-fold and 1.6–3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30–42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca²⁺ together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and β-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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7 pages, 1383 KiB

Open AccessArticle

(-)-Leucophyllone, a Tirucallane Triterpenoid from Cornus walteri, Enhances Insulin Secretion in INS-1 Cells

by Dahae Lee, Ki Hyun Kim, Taesu Jang and Ki Sung Kang

Plants 2021, 10(3), 431; https://doi.org/10.3390/plants10030431 - 24 Feb 2021

Cited by 2 | Viewed by 1783

Abstract

Phytochemical examination of the MeOH extract from the stems and stem bark of Cornus walteri (Cornaceae) led to the isolation and verification of a tirucallane triterpenoid, (-)-leucophyllone, as a major component. Its structure was elucidated using NMR spectroscopy and liquid chromatography–mass spectrometry. The [...] Read more.

Phytochemical examination of the MeOH extract from the stems and stem bark of Cornus walteri (Cornaceae) led to the isolation and verification of a tirucallane triterpenoid, (-)-leucophyllone, as a major component. Its structure was elucidated using NMR spectroscopy and liquid chromatography–mass spectrometry. The effect of (-)-leucophyllone on insulin secretion in INS-1 cells was investigated. (-)-Leucophyllone increased glucose-stimulated insulin secretion (GSIS) at concentrations showing no cytotoxic effect in rat INS-1 pancreatic β-cells. Moreover, we attempted to determine the mechanism of action of (-)-leucophyllone in the activation of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1). Treatment of INS-1 cells with (-)-leucophyllone markedly increased the expression of these proteins. Our findings indicate the potential of (-)-leucophyllone as an antidiabetic agent. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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12 pages, 2551 KiB

Open AccessArticle

Analgesic and Anti-Inflammatory Effects of Aucklandia lappa Root Extracts on Acetic Acid-Induced Writhing in Mice and Monosodium Iodoacetate-Induced Osteoarthritis in Rats

by Hee-Geun Jo, Geon-Yeong Lee, Chae Yun Baek, Ho Sueb Song and Donghun Lee

Plants 2021, 10(1), 42; https://doi.org/10.3390/plants10010042 - 26 Dec 2020

Cited by 11 | Viewed by 3501

Abstract

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, [...] Read more.

Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions. We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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12 pages, 1961 KiB

Open AccessArticle

New Eudesmane-Type Sesquiterpene Glycosides from the Leaves of Aster koraiensis

by Ji-Young Kim, Young Hye Seo, Im-Ho Lee, He Yun Choi, Hak Cheol Kwon, Jung-Hye Choi, Jun Lee and Dae Sik Jang

Plants 2020, 9(12), 1811; https://doi.org/10.3390/plants9121811 - 21 Dec 2020

Cited by 2 | Viewed by 2321

Abstract

Four new eudesmane-type sesquiterpenoids, (1R,5S,6R,7S,9S,10S)-1,6,9-trihydroxy-eudesm-3-ene-1,6-di-O-β-d-glucopyranoside (1), (1R,5S,6S,7R,9S,10S)-1,6,9,11-tetrahydroxy-eudesm-3-ene-1,6-di-O-β-d-glucopyranoside [...] Read more.

Four new eudesmane-type sesquiterpenoids, (1R,5S,6R,7S,9S,10S)-1,6,9-trihydroxy-eudesm-3-ene-1,6-di-O-β-d-glucopyranoside (1), (1R,5S,6S,7R,9S,10S)-1,6,9,11-tetrahydroxy-eudesm-3-ene-1,6-di-O-β-d-glucopyranoside (3), (1R,5S,6R,7S,9S,10R)-9-O-(Z-p-coumaroyl)-1,6,9-trihydroxy-eudesm-3-ene-6-O-β-d-glucopyranoside (6), and (1R,5S,6R,7S,9S,10R)-9-O-(E-feruloyl)-1,6,9-trihydroxy-eudesm-3-ene-6-O-β-d-glucopyranoside (7), were isolated from a 95% EtOH extract of the leaves of Aster koraiensis by repeated chromatography. Moreover, three sesquiterpenoids (2, 4, and 5) and two caffeoylquinic acids (8 and 9) having previously known chemical structures were isolated during the isolation procedure. The four new compounds (1, 3, 6, and 7) were elucidated by spectroscopic data (1D- and 2D-NMR, MS, and ECD) interpretation and hydrolysis. Moreover, the absolute configurations of 2, 4, and 5 were determined for the first time in this study. The compounds isolated were tested for their viability on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production on LPS-stimulated RAW 264.7 cells. Among them, only 7 presented weak inhibitory effects on both NO and PGE₂ production. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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21 pages, 6389 KiB

Open AccessArticle

Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies

by Jinkyung Lee, Quynh Nhu Nguyen, Jun Yeon Park, Sullim Lee, Gwi Seo Hwang, Noriko Yamabe, Sungyoul Choi and Ki Sung Kang

Plants 2020, 9(12), 1681; https://doi.org/10.3390/plants9121681 - 01 Dec 2020

Cited by 5 | Viewed by 2424

Abstract

Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An [...] Read more.

Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL A. absinthium extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the A. absinthium extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of A. absinthium extract and its mechanism of action against cisplatin-induced renal injury. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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15 pages, 1714 KiB

Open AccessArticle

Mechanisms of Antidiabetic Activity of Methanolic Extract of Punica granatum Leaves in Nicotinamide/Streptozotocin-Induced Type 2 Diabetes in Rats

by Shinu Pottathil, Parminder Nain, Mohamed A. Morsy, Jaspreet Kaur, Bandar E. Al-Dhubiab, Sandhya Jaiswal and Anroop B. Nair

Plants 2020, 9(11), 1609; https://doi.org/10.3390/plants9111609 - 19 Nov 2020

Cited by 26 | Viewed by 5260

Abstract

The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL [...] Read more.

The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL (100, 200, 400, and 600 mg/kg) were administered orally to diabetic rats for 45 days on a daily basis. The antidiabetic effect of MEPGL was examined by measuring blood glucose, plasma insulin, and glycated hemoglobin (HbA1c) levels, as well as with an oral glucose tolerance test. The antioxidant effect of MEPGL was determined by analyzing hepatic and renal antioxidant markers, namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation. The other biochemical markers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, and creatinine, as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. Type 2 diabetes significantly altered these parameters, while oral administration of the MEPGL significantly ameliorated them. Moreover, the pancreatic histopathological changes were attenuated with MEPGL treatment. In a nutshell, oral MEPGL administration in diabetic rats showed antidiabetic activity due to its antioxidant activity, most probably due to the gallic acid, ellagic acid, and apigenin found in MEPGL. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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26 pages, 4215 KiB

Open AccessArticle

Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals

by Prawej Ansari, Peter R. Flatt, Patrick Harriott and Yasser H.A. Abdel-Wahab

Plants 2020, 9(10), 1348; https://doi.org/10.3390/plants9101348 - 12 Oct 2020

Cited by 19 | Viewed by 4334

Abstract

Annona squamosa is generally referred to as a ‘custard apple’. Antidiabetic actions of hot water extract of Annona squamosa (HWAS) leaves together with isolation of active insulinotropic compounds were studied. Insulin release, membrane potential and intracellular Ca²⁺ were determined using BRIN-BD11 cells [...] Read more.

Annona squamosa is generally referred to as a ‘custard apple’. Antidiabetic actions of hot water extract of Annona squamosa (HWAS) leaves together with isolation of active insulinotropic compounds were studied. Insulin release, membrane potential and intracellular Ca²⁺ were determined using BRIN-BD11 cells and isolated mouse islets. 3T3L1 adipocytes and in vitro models were used to determine cellular glucose uptake, insulin action, starch digestion, glucose diffusion, DPP-IV activity and glycation. Glucose intolerant high-fat fed rats were used for in vivo studies. Active compounds were isolated and characterized by HPLC, LCMS and NMR. HWAS stimulated insulin release from clonal β-cells and mouse islets. Using fluorescent indicator dyes and modulators of insulin secretion, effects could be attributed to depolarization of β-cells and influx of Ca²⁺. Secretion was stimulated by isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, indicating additional non-K_ATP dependent pathways. Extract stimulated cellular glucose uptake and insulin action and inhibited starch digestion, protein glycation, DPP-IV enzyme activity and glucose diffusion. Oral HWAS improved glucose tolerance and plasma insulin in high-fat fed obese rats. Treatment for 9 days with HWAS (250 mg/5 mL/kg), partially normalised energy intake, body weight, pancreatic insulin content, and both islet size and beta cell mass. This was associated with improved oral glucose tolerance, increased plasma insulin and inhibition of plasma DPP-IV activity. Isolated insulinotropic compounds, including rutin (C₂₇H₃₀O₁₆), recapitulated the positive actions of HWAS on beta cells and in vivo glucose tolerance and plasma insulin responses. Annona squamosa is attractive as a dietary adjunct in treatment of T2DM and as a source of potential antidiabetic agents including rutin. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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23 pages, 4107 KiB

Open AccessArticle

Biochemical and Molecular Investigation of In Vitro Antioxidant and Anticancer Activity Spectrum of Crude Extracts of Willow Leaves Salix safsaf

by Mourad A. M. Aboul-Soud, Abdelkader E. Ashour, Jonathan K. Challis, Atallah F. Ahmed, Ashok Kumar, Amr Nassrallah, Tariq A. Alahmari, Quaiser Saquib, Maqsood A. Siddiqui, Yazeed Al-Sheikh, Hany A. El-Shemy, Ahmed M. Aboul-Enein, Khalid M. Alghamdi, Paul D. Jones and John P. Giesy

Plants 2020, 9(10), 1295; https://doi.org/10.3390/plants9101295 - 30 Sep 2020

Cited by 16 | Viewed by 4332

Abstract

Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the [...] Read more.

Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the MTT assay revealed that chloroform (CHCl₃) and ethyl acetate (EtOAc)-soluble fractions exhibited specific anticancer activities as marginal toxicities were observed against two non-cancerous control cell lines (BJ-1 and MCF-12). Ultra-high-resolution mass spectrometry Q-Exactive™ HF Hybrid Quadrupole-Orbitrap™ coupled with liquid chromatography (UHPLC) indicated that both extracts are enriched in features belonging to major phenolic and purine derivatives. Fluorescence-activated cell sorter analysis (FACS), employing annexin V-FITC/PI double staining indicated that the observed cytotoxic potency was mediated via apoptosis. FACS analysis, monitoring the increase in fluorescence signal, associated with oxidation of DCFH to DCF, indicated that the mechanism of apoptosis is independent of reactive oxygen species (ROS). Results of immunoblotting and RT-qPCR assays showed that treatment with organic fractions under investigation resulted in significant up-regulation of pro-apoptotic protein and mRNA markers for Caspase-3, p53 and Bax, whereas it resulted in a significant reduction in amounts of both protein and mRNA of the anti-apoptotic marker Bcl-2. FACS analysis also indicated that pre-treatment and co-treatment of human amniotic epithelial (WISH) cells exposed to the ROS H₂O₂ with EtOAc fraction provide a cytoprotective and antioxidant capacity against generated oxidative stress. In conclusion, our findings highlight the importance of natural phenolic and flavonoid compounds with unparalleled and unique antioxidant and anticancer properties. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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11 pages, 1726 KiB

Open AccessArticle

Chemical Constituents of the Leaves of Campanula takesimana (Korean Bellflower) and Their Inhibitory Effects on LPS-induced PGE₂ Production

by Yutong Qi, Se-In Choi, So-Ri Son, Hee-Soo Han, Hye Shin Ahn, Yu-Kyong Shin, Sun Hee Lee, Kyung-Tae Lee, Hak Cheol Kwon and Dae Sik Jang

Plants 2020, 9(9), 1232; https://doi.org/10.3390/plants9091232 - 18 Sep 2020

Cited by 6 | Viewed by 3143

Abstract

Campanula takesimana Nakai (Campanulaceae; Korean bellflower) is one of the endemic herbs of Korea. The plant has been used as traditional medicines for treating asthma, tonsillitis, and sore throat in Korea. A hot water extract of the leaves of C. takesimana exhibited a [...] Read more.

Campanula takesimana Nakai (Campanulaceae; Korean bellflower) is one of the endemic herbs of Korea. The plant has been used as traditional medicines for treating asthma, tonsillitis, and sore throat in Korea. A hot water extract of the leaves of C. takesimana exhibited a significant inhibitory effect on lipopolysaccharide (LPS)-stimulated prostaglandin E₂ (PGE₂) production. Repetitive chromatographic separation of the hot water extract led to the isolation of three new neolignan glucosides, campanulalignans A–C (1–3), with 15 known compounds (4–18). The structures of new compounds 1–3 were elucidated by analyzing nuclear magnetic resonance (NMR) spectroscopic data, along with high resolution quadrupole time of flight mass (HR-Q-TOF-MS) spectrometric data. Among the isolates, simplidin (7), 5-hydroxyconiferaldehyde (11), icariside F₂ (12), benzyl-α-l-arabinopyranosyl-(1″→6′)-β-d-glucopyranoside (13), and kaempferol 3-O-β-d-apiosyl (1→2)-β-d-glucopyranoside (15) were isolated from the Campanulaceae family for the first time. The isolates (1, 2, and 4–18) were assessed for their anti-inflammatory effects on LPS-stimulated PGE₂ production on RAW 264.7 cells. 7R,8S-Dihydrodehydrodiconiferyl alcohol (5), 3′,4-O-dimethylcedrusin 9-O-β-glucopyranoside (6), pinoresinol di-O-β-d-glucoside (8), ferulic acid (10), 5-hydroxyconiferaldehyde (11), and quercetin (18) showed significant inhibitory effects on LPS-stimulated PGE₂ production. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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12 pages, 3369 KiB

Open AccessArticle

Evaluation of Anti-Colitis Effect of KM1608 and Biodistribution of Dehydrocostus Lactone in Mice Using Bioimaging Analysis

by Sullim Lee, Sang-Back Kim, Jaemin Lee, Jimin Park, Sungyoul Choi, Gwi Seo Hwang, Han-Seok Choi and Ki Sung Kang

Plants 2020, 9(9), 1175; https://doi.org/10.3390/plants9091175 - 10 Sep 2020

Cited by 2 | Viewed by 2435

Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing disorder modulated by numerous factors. Recent failures of drugs targeting single factors suggest that multitargeting drugs could be useful for the treatment of IBD. Natural medicines may be an alternative option for the treatment of [...] Read more.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder modulated by numerous factors. Recent failures of drugs targeting single factors suggest that multitargeting drugs could be useful for the treatment of IBD. Natural medicines may be an alternative option for the treatment of IBD, owing to the complex nature of the disease. However, most natural medicines have poor in vitro and in vivo translational potential because of inadequate pharmacokinetic study. KM1608, a mixture of the medicinal plants Aucklandia lappa, Terminalia chebula, and Zingiber officinale, was examined for its anti-colitis effects and biodistribution using bioimaging. Dehydrocostus lactone, as a marker compound, was analyzed to assess the biodistribution of KM1608. KM1608 significantly attenuated the disease activity of dextran sodium sulfate-induced colitis in mice and suppressed inflammatory mediators such as myeloperoxidase, proinflammatory cytokines (TNF-α and IL-6), and the Th2-type cytokine IL-4 in the colon. Optical fluorescence imaging revealed that KM1608 was distributed in the intestinal area as a target organ. Collectively, our findings suggest that KM1608 is a potential therapeutic formulation for IBD. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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14 pages, 2774 KiB

Open AccessArticle

Bioactive Phytochemicals Isolated from Akebia quinata Enhances Glucose-Stimulated Insulin Secretion by Inducing PDX-1

by Dahae Lee, Jin Su Lee, Jurdas Sezirahiga, Hak Cheol Kwon, Dae Sik Jang and Ki Sung Kang

Plants 2020, 9(9), 1087; https://doi.org/10.3390/plants9091087 - 24 Aug 2020

Cited by 7 | Viewed by 2710

Abstract

Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-β-d-glucoside (1), three triterpenoids maslinic acid (2), [...] Read more.

Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-β-d-glucoside (1), three triterpenoids maslinic acid (2), scutellaric acid (3), and hederagenin (4), and three triterpenoidal saponins akebia saponin PA (5), hederacoside C (6), and hederacolchiside F (7) were isolated from a 70% EtOH extract of the fruits of A. quinata (AKQU). The chemical structures of isolates 1–7 were determined by analyzing the 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data. Here, we evaluated the effects of AKQU and compounds 1–7 on insulin secretion using the INS-1 rat pancreatic β-cell line. Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic β-cell function were detected by Western blotting. Among the isolates, stigmasterol-3-O-β-d-glucoside (1) exhibited strong GSIS activity and triggered the overexpression of pancreas/duodenum homeobox protein-1 (PDX-1), which is implicated in the regulation of pancreatic β-cell survival and function. Moreover, isolate 1 markedly induced the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), insulin receptor substrate-2 (IRS-2), phosphoinositide 3-kinase (PI3K), and Akt, which regulate the transcription of PDX-1. The results of our experimental studies indicated that stigmasterol-3-O-β-d-glucoside (1) isolated from the fruits of A. quinata can potentially enhance insulin secretion, and might alleviate the reduction in GSIS during the development of T2DM. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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9 pages, 920 KiB

Open AccessArticle

Three New Oleanane-Type Triterpenoidal Glycosides from Impatiens balsamina and Their Biological Activity

by Tae Hyun Lee, Won Se Suh, Lalita Subedi, Sun Yeou Kim, Sang Un Choi, Kang Ro Lee and Chung Sub Kim

Plants 2020, 9(9), 1083; https://doi.org/10.3390/plants9091083 - 24 Aug 2020

Cited by 10 | Viewed by 2697

Abstract

Three new oleanane-type triterpenoidal glycosides, imbalosides A–C (1–3), were isolated from the white flowers of Impatiens balsamina. The structures of these phytochemical constituents (1–3) were elucidated through 1D and 2D Nuclear Magnetic Resonance (NMR) [...] Read more.

Three new oleanane-type triterpenoidal glycosides, imbalosides A–C (1–3), were isolated from the white flowers of Impatiens balsamina. The structures of these phytochemical constituents (1–3) were elucidated through 1D and 2D Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) data analyses followed by chemical methods. All the characterized compounds (1–3) were evaluated for their antiproliferative activity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and BT549) and their anti-neuroinflammatory activity on the basis of inhibition levels of nitric oxide (NO) in the lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cell lines. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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11 pages, 2068 KiB

Open AccessArticle

Constituents of Gastrodia elata and Their Neuroprotective Effects in HT22 Hippocampal Neuronal, R28 Retinal Cells, and BV2 Microglial Cells

by Hye Mi Kim, Jaeyoung Kwon, Kyerim Lee, Jae Wook Lee, Dae Sik Jang and Hak Cheol Kwon

Plants 2020, 9(8), 1051; https://doi.org/10.3390/plants9081051 - 18 Aug 2020

Cited by 6 | Viewed by 3121

Abstract

Gastrodia elata is widely used in traditional medicine and contains various types of metabolites with pharmacological activity. In the course of searching for neuroprotective molecules associated with the potential of G. elata in the treatment of neurodegenerative disorders, two new phenolic compounds ( [...] Read more.

Gastrodia elata is widely used in traditional medicine and contains various types of metabolites with pharmacological activity. In the course of searching for neuroprotective molecules associated with the potential of G. elata in the treatment of neurodegenerative disorders, two new phenolic compounds (1 and 2) and a new tripeptide (3), together with 16 known compounds (4–19), were isolated from the rhizomes of G. elata. The structures of the compounds were determined by the interpretation of spectroscopic data, including nuclear magnetic resonance and mass spectrometry data. All obtained compounds were assessed for their ability to protect neuronal cells against neurotoxicity and neuroinflammation. Of these, 4 and 5 were found to possess moderate activities in HT22 hippocampal neuronal cells, whereas 2, 6, and 7 showed weak activities in R28 retinal cells. Additionally, compound 9 showed moderate inhibitory activity on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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10 pages, 1970 KiB

Open AccessCommunication

The Effects of Triterpenoid Saponins from the Seeds of Momordica cochinchinensis on Adipocyte Differentiation and Mature Adipocyte Inflammation

by Jae Sik Yu, Namood E. Sahar, Yan-Ran Bi, Kiwon Jung, Changhyun Pang, Joo Young Huh and Ki Hyun Kim

Plants 2020, 9(8), 984; https://doi.org/10.3390/plants9080984 - 03 Aug 2020

Cited by 4 | Viewed by 3518

Abstract

Obesity is a medical condition in which abnormal or excessive fat accumulates to an extent that is associated with various diseases. In our ongoing research to figure out natural products with anti-obesity effects, a phytochemical investigation of the EtOH extract of the seeds [...] Read more.

Obesity is a medical condition in which abnormal or excessive fat accumulates to an extent that is associated with various diseases. In our ongoing research to figure out natural products with anti-obesity effects, a phytochemical investigation of the EtOH extract of the seeds of Momordica cochinchinensis was carried out, which resulted in the isolation of two major triterpenoid saponins: gypsogenin 3-O-β-d-galactopyranosyl(1→2)-[α-l-rhamnopyranosyl (1→3)]-β-d-glucuronopyranoside (1) and quillaic acid 3-O-β-d-galactopyranosyl(1→2)-[α-l-rhamnopyranosyl(1→3)]-β-d-glucuronopyranoside (2). Then, the effects of the isolated triterpenoid saponins (1 and 2) on adipocyte differentiation were evaluated, and it was demonstrated that the isolated saponin (1) showed inhibitory effects on adipogenesis. In mature adipocytes, the isolated saponin (1) reversed tumor necrosis factor α (TNFα)-induced proinflammatory cytokine gene expression. Additionally, the isolated saponin (1) reduced lipolytic gene expression leading to decreased basal lipolysis activity. Collectively, these findings suggest that saponin (1) of M. cochinchinensis exerts beneficial effects in the regulation of adipogenesis and adipocyte inflammation and could be a potential therapeutic alternative in the treatment of obesity-induced metabolic diseases. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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13 pages, 3366 KiB

Open AccessArticle

Biocompatibility and Antimicrobial Activity of Reynoutria elliptica Extract for Dental Application

by Song-Yi Yang and Min-Kyung Kang

Plants 2020, 9(6), 670; https://doi.org/10.3390/plants9060670 - 26 May 2020

Cited by 5 | Viewed by 2343

Abstract

This study was conducted to determine whether nature-derived Reynoutria elliptica extracts exhibit biocompatibility and antimicrobial effects against oral pathogens such as Streptococcus mutans and Candida albicans. Fine particles of Reynoutria elliptica extract were used to probe for biocompatibility and antimicrobial activity toward [...] Read more.

This study was conducted to determine whether nature-derived Reynoutria elliptica extracts exhibit biocompatibility and antimicrobial effects against oral pathogens such as Streptococcus mutans and Candida albicans. Fine particles of Reynoutria elliptica extract were used to probe for biocompatibility and antimicrobial activity toward these pathogens, and results were evaluated with an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, spectrophotometric growth inhibitory assay, the total number of colony-forming units (CFU), an agar disk diffusion test, and scanning electron microscopy (SEM). In addition, UV/VIS spectroscopy was used to determine the levels of flavonoid and polyphenol in experimental solutions. Several experimental groups showed cell viability higher than 70%, and the antimicrobial activity toward both S. mutans and C. albicans was significantly higher than was that seen for the control group. In CFU and agar disk diffusion tests with C. albicans, increases in the concentration of Reynoutria elliptica extract led to significantly increased antimicrobial effects. Additionally, SEM results showed that Reynoutria elliptica extract changed the morphology and density of S. mutans and C. albicans. The results of this research can be applied to the use of Reynoutria elliptica extracts for the development of oral products that are biologically friendly and can control oral diseases such as dental caries and candida-associated denture stomatitis. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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Review

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14 pages, 325 KiB

Open AccessEditor’s ChoiceReview

Wound Healing Activities and Potential of Selected African Medicinal Plants and Their Synthesized Biogenic Nanoparticles

by Caroline Tyavambiza, Phumuzile Dube, Mediline Goboza, Samantha Meyer, Abram Madimabe Madiehe and Mervin Meyer

Plants 2021, 10(12), 2635; https://doi.org/10.3390/plants10122635 - 30 Nov 2021

Cited by 17 | Viewed by 5543

Abstract

In Africa, medicinal plants have been traditionally used as a source of medicine for centuries. To date, African medicinal plants continue to play a significant role in the treatment of wounds. Chronic wounds are associated with severe healthcare and socio-economic burdens despite the [...] Read more.

In Africa, medicinal plants have been traditionally used as a source of medicine for centuries. To date, African medicinal plants continue to play a significant role in the treatment of wounds. Chronic wounds are associated with severe healthcare and socio-economic burdens despite the use of conventional therapies. Emergence of novel wound healing strategies using medicinal plants in conjunction with nanotechnology has the potential to develop efficacious wound healing therapeutics with enhanced wound repair mechanisms. This review identified African medicinal plants and biogenic nanoparticles used to promote wound healing through various mechanisms including improved wound contraction and epithelialization as well as antibacterial, antioxidant and anti-inflammatory activities. To achieve this, electronic databases such as PubMed, Scifinder^® and Google Scholar were used to search for medicinal plants used by the African populace that were scientifically evaluated for their wound healing activities in both in vitro and in vivo models from 2004 to 2021. Additionally, data on the wound healing mechanisms of biogenic nanoparticles synthesized using African medicinal plants is included herein. The continued scientific evaluation of wound healing African medicinal plants and the development of novel nanomaterials using these plants is imperative in a bid to alleviate the detrimental effects of chronic wounds. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

35 pages, 2387 KiB

Open AccessReview

Plants of the Spontaneous Flora with Beneficial Action in the Management of Diabetes, Hepatic Disorders, and Cardiovascular Disease

by Maria Valentina Ignat, Teodora Emilia Coldea, Liana Claudia Salanță and Elena Mudura

Plants 2021, 10(2), 216; https://doi.org/10.3390/plants10020216 - 23 Jan 2021

Cited by 14 | Viewed by 5413

Abstract

The current pharmacological agents advised for the management of diabetes as well as cardiovascular and hepatic diseases are subject to numerous studies for safety and efficacy. Therefore, it is worth looking into alternative therapeutic aids such as natural products of medicinal plants. By [...] Read more.

The current pharmacological agents advised for the management of diabetes as well as cardiovascular and hepatic diseases are subject to numerous studies for safety and efficacy. Therefore, it is worth looking into alternative therapeutic aids such as natural products of medicinal plants. By a broad review of in vitro and in vivo studies on the various dandelion, chicory, and mulberry extracts, this work highlights their bioactive compounds and therapeutic action when used as a prevention and management aid in public health such as diabetes, cardiovascular disease, and hepatic disorders like non-alcoholic steatohepatitis. Natural products of dandelion leaves and root extracts can suppress the development of liver cancer, decrease insulin resistance, and suppress total triglyceride and cholesterol levels. Recent studies on mulberry leaves extracts indicated that they could decrease palmitic acid-induced lipotoxicity, increase total cholesterol and bile acid excretion, improve superoxide dismutase expression, and improve insulin resistance. Chicory root extracts boost satiety, reverse insulin resistance, and augment lipid metabolism thanks to their contents in chicoric acid, chlorogenic acid, and polysaccharides. Taraxacum officinale L., Morus nigra L., and Cichorium intybus L. present hepatoprotective, anti-inflammatory, antioxidant, hypolipidemic, and hypoglycemic activities and are shown to be advantageous in the management of obesity, dyslipidemia, Type 2 diabetes, and non-alcoholic fatty liver diseases. These plants are commonly available in the European spontaneous flora and more attention could be paid to their natural products. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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27 pages, 5837 KiB

Open AccessReview

Therapeutic Application of Betalains: A Review

by Elaheh Madadi, Sahand Mazloum-Ravasan, Jae Sik Yu, Ji Won Ha, Hamed Hamishehkar and Ki Hyun Kim

Plants 2020, 9(9), 1219; https://doi.org/10.3390/plants9091219 - 17 Sep 2020

Cited by 59 | Viewed by 8582

Abstract

Anthocyanins, betalains, riboflavin, carotenoids, chlorophylls and caramel are the basic natural food colorants used in modern food manufacture. Betalains, which are composed of red–violet betacyanin and yellow betaxanthins, are water-soluble pigments that color flowers and fruits. Betalains are pigments primarily produced by plants [...] Read more.

Anthocyanins, betalains, riboflavin, carotenoids, chlorophylls and caramel are the basic natural food colorants used in modern food manufacture. Betalains, which are composed of red–violet betacyanin and yellow betaxanthins, are water-soluble pigments that color flowers and fruits. Betalains are pigments primarily produced by plants of the order Caryophyllales. Because of their anti-inflammatory, cognitive impairment, anticancer and anti-hepatitis properties, betalains are useful as pharmaceutical agents and dietary supplements. Betalains also exhibit antimicrobial and antimalarial effects, and as an example, betalain-rich Amaranthus spinosus displays prominent antimalarial activity. Studies also confirmed the antidiabetic effect of betalains, which reduced glycemia by 40% without causing weight loss or liver impairment. These findings show that betalain colorants may be a promising alternative to the synthetic dyes currently used as food additives. Full article

(This article belongs to the Special Issue Structurally and/or Biologically Novel Natural Products from Medicinal Plants)

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