Abstract
Introduction
Oxidative stress is included in the most potential triggers of metabolic diseases and diabetes mellitus (DM) progression.1,2 Increased and irregular synthesis of reactive oxygen species (ROS) and reactive nitrogen species explicitly results in oxidative stress, overloading the instinct antioxidant systems of the body and possibly exacerbating the conditions of DM.1,2 Furthermore, hyperglycemia is a pathogenically indicating condition in patients with DM, which originates from insufficient secretion of insulin or insulin resistance of target tissues. 3 Long-term excessive level of glucose in the bloodstream leads to multimetabolomic disorders of carbohydrates, protides, and lipids, which directly damage essential organs. 3 Taking part in the glucose intake process, the enzyme α-glucosidase cleaves subjected di- and oligosaccharides to produce glucose, initiating the absorption of glucose through the gut lumen. 4 Hence, the search for natural α-glucosidase inhibitors and ROS neutralizers became already a hotspot in DM drug research, as suppression of α-glucosidase activity and neutralization of ROS could potentially relieve severe exacerbation of DM. As part of our ongoing research for candidates of DM drug from native medicinal plants in Central Vietnam, a phytochemical study accompanied with screening for biological activities on Distichochlamys citrea M.F. Newman rhizomes was carried out. 5 The plant D. citrea is native to the central region of Vietnam, where it was discovered in Thua Thien Hue, Quang Binh, Quang Tri, Quang Nam, and Nghe An Provinces.6–8 Up to now, the investigations of chemical profiles and the biological activities of D. citrea have been limited. In addition, recent studies on this plant are scarcely available despite raising scientific interest in the genus Distichochlamys, except for reports on compositions and biological activities of the essential oils such as anti-inflammation and anticancer,9,10 and our previous study on the corresponding subject which reported that the ethyl acetate (EtOAc) fraction apparently exhibited both α-glucosidase inhibitory effect (IC50 = 115.75 µg/mL) and antioxidant potential via 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity (IC50 = 90.27 µg/mL). 5 This study was carried out to isolate and determine the corresponding bioactivities of phyto-constituents from potential fractions of D. citrea. The present study reports the isolation, α-glucosidase inhibitory activities, and DPPH scavenging capacities of 7 compounds from D. citrea rhizomes.
Results and Discussion
Determination of Isolated Compounds
Bioactivity-guided isolation of the extract of D. citrea rhizomes led to the identification of 7 known compounds comprising 2 flavonoids, 2 phenolics, 2 phytosterols, and 1 monoglyceride. Their chemical structures were elucidated based on a comparison of their spectroscopic data (ESI-mass spectrometry [MS], HR-ESI-MS, 1D- and 2D-nuclear magnetic resonance [NMR]) with those of the literature. These compounds were 5-hydroxy-37,4′-trimethoxyflavone (

Chemical structures of seven compounds
Antioxidant Activity Assay
The evaluation of the antioxidant activity of seven compounds showed that compound
α-Glucosidase Inhibitory Assay
As shown in Table S2, the isolated compounds all showed α-glucosidase inhibitory effects. Compound
In previous studies, 5-hydroxy-37,4′-trimethoxyflavone has been reported to have antioxidant, α-glucosidase inhibitor,18,19 antibacterial,
20
and anti-inflammatory properties.
21
The present results show that the antioxidant capacity of compound
The antioxidant activity as well as the free radical scavenging capacity of kaempferol (
Diarylheptanoids are found mainly in several species of the genera Alpinia, Zingiber, Curcuma, Alnus, Amomum, and Myrica.13,30–32 One of those diarylheptanoids, platyphyllone (
In previously reported studies, 5-O-caffeoylquinic acid (
β-Sitosterol (
Glycerol monostearate (
In conclusion, D. citrea has antioxidant and α-glucosidase inhibitory effects, providing scientific evidence for the use of D. citrea by Pako people in particular and in folk in general to treat inflammation and diabetes. These effects may be due to the presence of compounds such as kaempferol, 5-hydroxy-3,7,4'-trimethoxyflavone, platyphyllone, 5-O-caffeoylquinic acid, a mixture of β-sitosterol and stigmasterol, and glycerol monostearate. Furthermore, these compounds were isolated for the first time from the rhizome of D. citrea. The results suggest that D. citrea is a good source of antidiabetic, antioxidant, and anti-inflammatory agents, but further research is needed to elucidate their mechanism of action.
Materials and Methods
General Experimental Procedures
See Supplemental Material for further information. Plant Materials
The rhizomes of D. citrea M.F. Newman were collected in Bach Ma National Park, Thua Thien Hue Province, Vietnam in October 2019 and identified by Assoc. Prof. Truong Thi Bich Phuong (Department of Biology, University of Sciences, Hue University). A voucher specimen (DC-10.19) has been stored at the Laboratory of the Traditional Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam.5,53
Extraction and Isolation
See Supplemental Material for further information.
5-hydroxy-3,7,4'-trimethoxyflavone (
HR-ESI-MS m/z: 329.1029 [M + H]+ (calcd. for C18H17O6+, 329.1020).
1H NMR (δH, DMSO-d6, 600 MHz): 12.63 (1H, s, 5-OH), 8.06 (2H, d, J = 9.0 Hz, H-2′/H-6′), 7.14 (2H, d, J = 9.0 Hz, H-3′/H-5′), 6.76 (1H, d, J = 1.8 Hz, H-8), 6.38 (1H, d, J = 2.4 Hz, H-6), 3.86 (6H, s, 7-OCH3/4′-OCH3), and 3.81 (3H, s, 3-OCH3); 13C NMR (δC, DMSO-d6, 150 MHz): 178.1 (C-4), 165.2 (C-7), 161.4 (C-4′), 160.9 (C-5), 156.3 (C-9), 155.5 (C-2), 138.1 (C-3), 130.0 (C-2′/C-6′), 122.1 (C-1′), 114.2 (C-3′/C-5′), 105.2 (C-10), 97.8 (C-6), 92.4 (C-8), 59.7 (3-OCH3), 56.1 (7-OCH3), and 55.4 (4′-OCH3).
Kaempferol (
ESI-MS m/z: 284.8 [M-H]–.
1H NMR (δH, DMSO-d6, 600 MHz): 12.46 (1H, s, 5-OH), 10.79 (1H, s, 7-OH), 10.10 (1H, s, 3-OH), 9.35 (1H, s, 4′-OH), 8.04 (2H, d, J = 9.0 Hz, H-2′/H-6′), 6.92 (2H, d, J = 9.0 Hz, H-3′/H-5′), 6.44 (1H, d, J = 1.8 Hz, H-8), and 6.19 (1H, d, J = 1.8 Hz, H-6); 13C NMR (δC, DMSO-d6, 150 MHz): 175.9 (C-4), 163.9 (C-7), 160.7 (C-9), 159.2 (C-4′), 156.2 (C-5), 146.8 (C-2), 135.6 (C-3), 129.5 (C-2′/C-6′), 121.7 (C-1′), 115.4 (C-3′/C-5′), 103.1 (C-10), 98.2 (C-6), and 93.5 (C-8).
Platyphyllone (
ESI-MS m/z: 315.0 [M + H]+.
1H NMR (δH, CD3OD, 600 MHz): 7.01 (4H, d, J = 8.4 Hz, H-2′/H-6′/H-2′′/H-6′′), 6.71 (2H, d, J = 8.4 Hz, H-3′′/H-5′′), 6.70 (2H, d, J = 8.4 Hz, H-3′/H-5′), 4.04-4.00 (1H, m, H-5), 2.78-2.73 (4H, m, H-1/H-2), 2.67-2.64 (1H, m, Ha-7), 2.62-2.53 (2H, m, H-4), 2.56-2.52 (1H, m, Hb-7), and 1.70-1.66 (2H, m, H-6); 13C NMR (δC, CD3OD, 150 MHz): 211.9 (C-3), 156.6 (C-4′′), 156.4 (C-4′), 134.1 (C-1′′), 133.3 (C-1′), 130.3 (C-2′/C-6′/C-2′′/C-6′′), 116.2 (C-3′′/C-5′′), 116.1 (C-3′/C-5′), 68.3 (C-5), 51.3 (C-4), 46.4 (C-2), 40.5 (C-6), 31.9 (C-7), and 29.8 (C-1).
5-O-caffeoylquinic acid (
ESI-MS m/z: 191.8 [M-caffeoyl-H] –.
1H NMR (δH, CD3OD, 600 MHz): 7.58 (1H, d, J = 16.0 Hz, H-7′), 7.08 (1H, d, J = 1.8 Hz, H-2′), 6.98 (1H, dd, J = 7.8, 1.8 Hz, H-6′), 6.80 (1H, d, J = 7.8 Hz, H-5′), 6.28 (1H, d, J = 16.0 Hz, H-8′), 5.35 (1H, td, J = 9.0, 4.2 Hz, H-5), 4.20-4.17 (1H, m, H-3), 3.75 (1H, dd, J = 8.4, 3.0 Hz, H-4), 2.26-2.23 (1H, m, Ha-6), 2.21-2.18 (1H, m, Ha-2), 2.12-2.09 (1H, m, Hb-6), 2.08-2.05 (1H, m, Hb-2); 13C NMR (δC, CD3OD, 150 MHz): 177.0 (C-7), 168.7 (C-9′), 149.6 (C-4′), 147.1 (C-7′), 146.8 (C-3′), 127.8 (C-1′), 123.0 (C-6′), 116.5 (C-5′), 115.2 (C-2′), 115.3 (C-8′), 76.1 (C-1), 73.5 (C-4), 72.0 (C-5), 71.3 (C-3), 38.8 (C-6), 38.2 (C-2).
A mixture of β-sitosterol (
ESI-MS, 1H NMR (δH, CDCl3, 600 MHz), 13C NMR (δC, CDCl3, 150 MHz) data shown in Figures S29 to S32 (Supplemental Material).
Glycerol monostearate (
ESI-MS m/z: 356.8 [M-H]– ; 338.6 [M-H2O-H]– ; 320.6 [M-2H2O-H]–.
1H NMR (δH, CDCl3, 600 MHz): 4.21 (1H, dd, J = 11.4, 4.8 Hz, Ha-1′), 4.15 (1H, dd, J = 11.4, 6.0 Hz, Hb-1′), 3.93 (1H, t, J = 5.0 Hz, H-2′), 3.69 (1H, dd, J = 11.4, 5.0 Hz, Ha-3′), 3.60 (1H, dd, J = 11.4, 5.0 Hz, Hb-3′), 2.35 (2H, t, J = 7.5 Hz, H-2), 1.64-1.60 (2H, m, H-3), 1.38-1.20 (28H, brm, H-4 to H-17, overlapped), 0.88 (3H, t, J = 7.2 Hz, H-18); 13C NMR (δC, CDCl3, 150 MHz): 174.4 (C-1), 70.3 (C-2′), 65.2 (C-1′), 63.4 (C-3′), 34.2 (C-2), 31.9-29.1 and 22.7 (C-4 to C-17, overlapped), 24.9 (C-3), and 14.1 (C-18).
Antioxidant Activity Assay
See Supplemental Material for further information. α-Glucosidase Inhibitory Assay
See Supplemental Material for further information. Conclusions
This study provides information on the isolated chemical compounds from D. citrea rhizomes and their biological activities. Specifically, seven known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (
Supplemental Material
sj-docx-1-npx-10.1177_1934578X231177878 - Supplemental material for Phytochemical Constituents Isolated From Distichochlamys citrea M.F. Newman Rhizomes and Their Antioxidant and α-glucosidase Inhibitory Activities
Supplemental material, sj-docx-1-npx-10.1177_1934578X231177878 for Phytochemical Constituents Isolated From Distichochlamys citrea M.F. Newman Rhizomes and Their Antioxidant and α-glucosidase Inhibitory Activities by Tran Van Chen, Cao Ly Tan Thong, Hieu Tran-Trung and Nguyen Thi Ai Nhung, Nguyen Thanh Triet in Natural Product Communications
Footnotes
Acknowledgments
The authors would like to thank the partial facility support of the Faculty of Traditional Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, and ChenPharm's Lab for this study.
Author Contribution
Research idea was provided by NT Triet and TV Chen. Isolation and in vitro experiments were carried out by TV Chen and CLT Thong. Strutural elucidation and writing were done by TV Chen, TT Hieu and CLT Thong. Reading and revising the manuscript were done by NT Triet, TV Chen, TT Hieu and NTAN.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
