Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes
<i>Morus alba</i> (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from <i>M. al...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/4/526 |
| _version_ | 1797538199724097536 |
|---|---|
| author | Sung Ho Lim Jae Sik Yu Ho Seon Lee Chang-Ik Choi Ki Hyun Kim |
| author_facet | Sung Ho Lim Jae Sik Yu Ho Seon Lee Chang-Ik Choi Ki Hyun Kim |
| author_sort | Sung Ho Lim |
| collection | DOAJ |
| description | <i>Morus alba</i> (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from <i>M. alba</i> and their underlying mechanisms of action. Consequently, in this study, the fruits of <i>M. alba</i> were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of <i>M. alba</i> fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in <i>M. alba</i> fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D. |
| first_indexed | 2024-03-10T12:27:09Z |
| format | Article |
| id | doaj.art-8f0f170cc2d7404eac4f4e90eb4a68d5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T12:27:09Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8f0f170cc2d7404eac4f4e90eb4a68d52023-11-21T14:56:31ZengMDPI AGPharmaceutics1999-49232021-04-0113452610.3390/pharmaceutics13040526Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 AdipocytesSung Ho Lim0Jae Sik Yu1Ho Seon Lee2Chang-Ik Choi3Ki Hyun Kim4BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaIntegrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, KoreaIntegrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea<i>Morus alba</i> (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from <i>M. alba</i> and their underlying mechanisms of action. Consequently, in this study, the fruits of <i>M. alba</i> were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of <i>M. alba</i> fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in <i>M. alba</i> fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D.https://www.mdpi.com/1999-4923/13/4/526type 2 diabetes<i>Morus alba</i>rutinquercetin-3-<i>O</i>-β-<span style="font-variant: small-caps">d</span>-glucosideglucose uptakelipid accumulation |
| spellingShingle | Sung Ho Lim Jae Sik Yu Ho Seon Lee Chang-Ik Choi Ki Hyun Kim Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes Pharmaceutics type 2 diabetes <i>Morus alba</i> rutin quercetin-3-<i>O</i>-β-<span style="font-variant: small-caps">d</span>-glucoside glucose uptake lipid accumulation |
| title | Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes |
| title_full | Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes |
| title_fullStr | Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes |
| title_full_unstemmed | Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes |
| title_short | Antidiabetic Flavonoids from Fruits of <i>Morus alba</i> Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes |
| title_sort | antidiabetic flavonoids from fruits of i morus alba i promoting insulin stimulated glucose uptake via akt and amp activated protein kinase activation in 3t3 l1 adipocytes |
| topic | type 2 diabetes <i>Morus alba</i> rutin quercetin-3-<i>O</i>-β-<span style="font-variant: small-caps">d</span>-glucoside glucose uptake lipid accumulation |
| url | https://www.mdpi.com/1999-4923/13/4/526 |
| work_keys_str_mv | AT sungholim antidiabeticflavonoidsfromfruitsofimorusalbaipromotinginsulinstimulatedglucoseuptakeviaaktandampactivatedproteinkinaseactivationin3t3l1adipocytes AT jaesikyu antidiabeticflavonoidsfromfruitsofimorusalbaipromotinginsulinstimulatedglucoseuptakeviaaktandampactivatedproteinkinaseactivationin3t3l1adipocytes AT hoseonlee antidiabeticflavonoidsfromfruitsofimorusalbaipromotinginsulinstimulatedglucoseuptakeviaaktandampactivatedproteinkinaseactivationin3t3l1adipocytes AT changikchoi antidiabeticflavonoidsfromfruitsofimorusalbaipromotinginsulinstimulatedglucoseuptakeviaaktandampactivatedproteinkinaseactivationin3t3l1adipocytes AT kihyunkim antidiabeticflavonoidsfromfruitsofimorusalbaipromotinginsulinstimulatedglucoseuptakeviaaktandampactivatedproteinkinaseactivationin3t3l1adipocytes |