Front. Pharmacol. Frontiers in Pharmacology Front. Pharmacol. 1663-9812 Frontiers Media S.A. 1364948 10.3389/fphar.2024.1364948 Pharmacology Review Comprehensive overview of different medicinal parts from Morus alba L.: chemical compositions and pharmacological activities Wang et al. 10.3389/fphar.2024.1364948 Wang Yumei 1 † Ai Qing 1 2 † Gu Meiling 1 2 Guan Hong 3 Yang Wenqin 3 Zhang Meng 1 2 Mao Jialin 1 Lin Zhao 1 Liu Qi 1 * Liu Jicheng 1 * 1 The Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, China 2 School of Pharmacy, Qiqihar Medical University, Qiqihar, China 3 Office of Academic Research, Qiqihar Medical University, Qiqihar, China

Edited by: Karim Hosni, Institut National de Recherche et d’Analyse Physico-Chimique (INRAP), Tunisia

Reviewed by: Yeong-Geun Lee, Kyung Hee University, Republic of Korea

Chanin Sillapachaiyaporn, Karolinska Institutet (KI), Sweden

 *Correspondence: Qi Liu, liuqi_hlj@163.com; Jicheng Liu, jcliu@qmu.edu.cn

These authors have contributed equally to this work

 17 04 2024 2024 15 1364948 19 01 2024 25 03 2024 Copyright © 2024 Wang, Ai, Gu, Guan, Yang, Zhang, Mao, Lin, Liu and Liu. 2024 Wang, Ai, Gu, Guan, Yang, Zhang, Mao, Lin, Liu and Liu

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Morus alba L., a common traditional Chinese medicine (TCM) with a centuries-old medicinal history, owned various medicinal parts like Mori folium, Mori ramulus, Mori cortex and Mori fructus. Different medical parts exhibit distinct modern pharmacological effects. Mori folium exhibited analgesic, anti-inflammatory, hypoglycemic action and lipid-regulation effects. Mori ramulus owned anti-bacterial, anti-asthmatic and diuretic activities. Mori cortex showed counteraction action of pain, inflammatory, bacterial, and platelet aggregation. Mori fructus could decompose fat, lower blood lipids and prevent vascular sclerosis. The main chemical components in Morus alba L. covered flavonoids, phenolic compounds, alkaloids, and amino acids. This article comprehensively analyzed the recent literature related to chemical components and pharmacological actions of M. alba L., summarizing 198 of ingredients and described the modern activities of different extracts and the bioactive constituents in the four parts from M. alba L. These results fully demonstrated the medicinal value of M. alba L., provided valuable references for further comprehensive development, and layed the foundation for the utilization of M. alba L.

 Mori folium Mori ramulus Mori cortex Mori fructus chemical constituents pharmacological activities section-at-acceptance Ethnopharmacology 1 Introduction

Morus alba L., a deciduous tree species, belonging to the Moraceae family and Morus genus. China is the relatively early known country raising silkworms and growing M. alba L. The presence of M. alba L. could be traced back to thousands of years ago (Zeng et al., 2022). Besides, many medical classics such as Shennong Ben Cao, Tang Ben Cao and Ben Cao Gang Mu also recorded it (Wenmin Du, 2022). For the past few years, dozens of varieties of M. alba L. were widely planted in China, including cultivated and wild species (Ai et al., 2021). In TCM, M. alba L. is regarded as a treasure due to the rich active ingredients and modern activities of its different parts.

Mori cortex and Mori fructus taste slight cool and sweet. Mori cortex could purge and promoting water, relieve cough and asthma, reduce blood pressure, and against inflammatory (Batiha et al., 2023). Mori fructus could nourish blood and enhance immune function. Mori ramulus, which is mild and taste a litter bitter, owned functions of dispelling wind dampness and promoting blood circulation. Mori folium is a slight muted and possessed effects of dispelling wind, clearing heat, cooling blood, and improving eyesight. Mori fructus and Mori folium exhibit both medicinal and edible properties, making them widely used in medicine and food fields (Maqsood et al., 2022). In some Asian countries, Mori folium is used as a nutritional supplement (Liu et al., 2024). In South Korea, it is widely used as one ingredient of ice cream (Polumackanycz et al., 2021). In Japan, it is used as an anti-hyperglycemic supplement for the treatment of diabetes (Suthamwong et al., 2020). Recently, with the deepening awareness of M. alba L., its role in lowering blood sugar, alleviating depression, antioxidant and liver protection have been widely concerned.

The current pharmacological researches on M. alba L. mainly focus on Mori folium, Mori ramulus, Mori cortex and Mori fructus. With the rapid advance of science and technology, more bioactive substances covered flavonoids, alkaloids and phenols from M. alba L. were identified. In addition, there were several same biological active ingredients and some unique chemical components from different parts of M. alba L., the compositions were closely relevant to the pharmacological activities of each part. For example, 1-deoxynojirimycin, an alkaloid component only found in M. alba L., was the characteristic component with high-content from Mori folium, owns the intense inhibitory effect on α-glucosidase and exhibit obvious action in lowering blood glucose (Wang Shirui, 2023). Besides, on account of other affluent ingredients like proteins, carbohydrates, vitamins, trace elements and dietary fibre, Mori folium was also recognized as a high-quality food or mulberry tea (Polumackanycz et al., 2021). Thus it could be seen that due to the multifarious functional materials and particular pharmacological characteristics, different parts of M. alba L. maybe owned broad research prospects and were widely used in various scopes like medicine, food, and other fields (Maqsood et al., 2022).

On account of the favourable value of M. alba L., this review aimed to summarize the chemical components and the pharmacologic bioactivities of M. alba L., including Mori folium, Mori ramulus, Mori cortex and Mori fructus. The overall data in this present paper, could provide a helpful reference for further development and comprehensive utilization of M. alba L.

 2 Chemical profiles of <italic>Morus alba</italic> L

Up to 198 active compounds have been identified in the different parts of M. alba L. (Supplementary Table S1; Tables 1–7). Their structures are summarized in Figures 1–8.

Alkaloid in Morus alba L.

No. Sequential number Name Source Pharmacological properties Reference
1 141 fagomine B anti-obesity; anti-inflammatory D'Urso et al. (2019)
Ramos-Romero et al. (2022)
2 142 morusimic acid B B __ D'Urso et al. (2019)
3 143 morusimic acid C B __ D'Urso et al. (2019)
4 144 morusimic acid E B __ D'Urso et al. (2019)
5 145 1-deoxynojirimycin A; B antidiabetic D'Urso et al. (2019)
Asai et al. (2011)
6 146 1,4-dideoxy-1,4-imino-D-arabinitol D hyperamnesia Lei et al. (2022)
Gibbs (2016)
7 147 2-formyl-1H-pyrrole-1-butanoic acid B __ D'Urso et al. (2019)
8 148 3-epi-fagomine A anticancer; neuroprotection Amezqueta et al. (2012)
Zabady et al. (2022)
Bhuiyan et al. (2011)

Note: A, Mori folium; B, Mori fructus; C, Mori cortex; D, Mori ramulus.

Coumarins in Morus alba L.

No. Sequential number Name Source Pharmacological property Reference
1 149 aesculetin A anti-inflammatory Li et al. (2020)
2 150 coumarin C anticancer; anti-inflammatory Kavitha and Geetha (2018)
Bhattarai et al. (2021)
3 151 mulberroside B C anti-obesity Yang et al. (2011)
4 152 scopoletin A anti-inflammatory Li et al. (2020)
5 153 scopolin D anti-inflammatory; anti-hyperuricemic Yao et al. (2019)
Li et al. (2020)
6 154 skimmin A cardioprotection Doi et al. (2001)
Su et al. (2023)
7 155 umbelliferone C antidiabetic nephropathy Hyun et al. (2021)
Jin and Chen (2022)
8 156 5,7-dihydroxycoumarin 7-O-β-d-apiofuranosyl-(1→6)-O-β-d-glucopyranoside C anti-obesity Yang et al. (2011)
9 157 5,7-dihydroxycoumarin 7-O-β-D-glucopyranoside C anti-obesity Yang et al. (2011)

Note: A, Mori folium; B, Mori fructus; C, Mori cortex; D, Mori ramulus.

Carbohydrates in Morus alba L.

No. Sequential number Name Source Pharmacological property Reference
1 158 adenosine C anti-obesity Yang et al. (2011)
2 159 arabinose A anti-obesity Zhao et al. (2022)
3 160 D-galactose A anti-obesity Zhao et al. (2022)
4 161 D-galacturonic acid A anti-obesity Zhao et al. (2022)
5 162 D-glucose A anti-obesity Zhao et al. (2022)
6 163 D-glucuronic acid A anti-obesity Zhao et al. (2022)
7 164 D-mannose A anti-obesity Zhao et al. (2022)
8 165 fucose A anti-obesity Zhao et al. (2022)
9 166 L-rhamnose A anti-obesity Zhao et al. (2022)

Note: A, Mori folium; B, Mori fructus; C, Mori cortex; D, Mori ramulus.

Terpenoids in Morus alba L.

No. Sequential number Name Source Pharmacological property Reference
1 167 betulinic acid C anticancer; anti-obesity Yang et al. (2011)
Aswathy et al. (2022)
2 168 grasshopper ketone B anti-inflammatory Lee et al. (2021b)
3 169 lanosterol acetate A antigout Oh et al. (2021)
4 170 loliolide A antidiabetic; anti-inflammatory; anti-aging Hunyadi et al. (2013)
Park et al. (2019)
5 171 roseoside B anti-inflammatory D'Urso et al. (2019)
Wang et al. (2023b)
6 172 ursolic acid C; D anti-inflammatory; antioxidant; antiviral Yang et al. (2011)
Liu Ying (2023)
Al-Kuraishy et al. (2022)
Kornel et al. (2023)
7 173 uvaol C anti-obesity Yang et al. (2011)
anticancer Bonel-Perez et al. (2020)
8 174 7-ketositosterol B kidney protection Lee et al. (2021b)
9 175 β-sitosterol C anti-obesity; anticancer Yang et al. (2011)
Khan et al. (2022)

Note: A, Mori folium; B, Mori fructus; C, Mori cortex; D, Mori ramulus.

Organic acids in Morus alba L.

No. Sequential number Name Source Pharmacological property Reference
1 176 Acetic acid A skin protectant Chen et al. (2021)
2 177 citric acid A immuno-enhancement Chen et al. (2021)
Hu et al. (2024)
3 178 fumaric acid A anticancer Chen et al. (2021)
Das et al. (2016)
4 179 lactic acid A anti-inflammatory; anticancer Chen et al. (2021)
Zhou et al. (2022a)
5 180 malic acid A antioxidant; liver protection Chen et al. (2021)
Koriem and Tharwat (2023)
6 181 succinic acid A anticancer Chen et al. (2021)
Kasarci et al. (2021)

Note: A, Mori folium; B, Mori fructus; C, Mori cortex; D, Mori ramulus.

Anthocyanins in Morus alba L.

No. Sequential number Name Source Pharmacological property Reference
1 182 anthocyanins B antioxidant; antibacterial D'Urso et al. (2019)
Suriyaprom et al. (2021)
2 183 cyanidin-3-glucoside B anticancer Zabady et al. (2022)
3 184 cyanidin-3-O-glucoside B anticancer Chen et al. (2022c)
Wei et al. (2021)
4 185 cyanidin-3-O-rutinoside B antioxidant Chen et al. (2022d)
Delazar et al. (2010)

Note: A, Mori folium; B, Mori fructus; C, Mori cortex; D, Mori ramulus.

Other constituents in Morus alba L.

No. Sequential number Name Category Source Pharmacological property Reference
1 186 butyl pyroglutamate amino acid derivatives B kidney protection Lee et al. (2018)
2 187 γ-aminobutyric acid amino acids A antifatigue Chen et al. (2016)
3 188 L-proline amino acids B anti-inflammatory; kidney protection Lee et al. (2021b)
Li et al. (2019)
4 189 L-tryptophan amino acids A antipyretic; mood improvement; sleep improvement Qu et al. (2019)
Sutanto et al. (2022)
Kikuchi et al. (2021)
5 190 chalcomoracin Diels–Alder adducts A anti-bacteria Jeon and Choi (2019)
Kim et al. (2012)
6 191 guangsangon E Diels–Alder adducts A anticancer Shu et al. (2021)
7 192 isobavachalcone chalcones B antidiabetic; antioxidant; anti-inflammatory; neuroprotection; antimicrobial Wang et al. (2013)
Wang et al. (2021)
8 193 morachalcone A chalcones D anti-melanogenesis Zhang et al. (2016)
9 194 2,4,2′,4′-tetrahydroxychalcone chalcones D anti-melanogenesis Zhang et al. (2016)
10 195 lignin phenylpropanoids A anti-microbial Chao et al. (2021)
Das et al. (2024)
11 196 melatonin amines A antioxidant; anticancer; anti-aging Panyatip et al. (2022)
Bhattacharya et al. (2019)
12 197 vitamin E vitamins C antioxidant; anti-inflammatory Kavitha and Geetha (2018)
13 198 cyclo (L-Pro-L-Val) peptides B anti-inflammatory Lee et al. (2021b)

Note: A, Mori folium; B, Mori fructus; C, Mori cortex; D, Mori ramulus.

Phenols.

Alkaloids.

Coumarins.

Carbohydrates.

Terpenoids.

Organic acids.

Anthocyanin.

Other categories.

 3 The pharmacological activities of components in <italic>Morus alba</italic> L 3.1 Hypoglycemic activity

1-deoxynojirimycin was the important active ingredient in M. alba L. Researchers have confirmed that 1-deoxynojirimycin exhibit an inhibitory effect on α-glucosidase, further reduced the postprandial blood glucose in pre-diabetic and mildly diabetic individuals (Asai et al., 2011). Current evidence showed that the same dose of Mori folium has similar biological activities like lowering blood sugar and protecting kidney in diabetic patient as the purified 1-deoxynojirimycin (Huang et al., 2014). In addition, Mori ramulus extract was reported effective hypoglycemic action and well inhibition of PTP1B and α-glucosidase, the main components were oxyresveratrol and kuwanon G (Kwon et al., 2022). Compared with Mori folium and Mori fructus, the hypoglycemic effects of Mori ramulus and Mori cortex were much more significant (Zhou Q. Y. et al., 2022). The various bioactive components of medicinal parts from M. alba L. expressed multiple antidiabetic targets and less adverse reactions. Thanks to the favourable hypoglycemic effect and the accessibility of M. alba L. resources, M. alba L. may exhibit a promising prospect in the preventing and treating of diabetes. The main hypoglycemic compounds in M. alba L. and their mechanisms are shown in Table 8.

Hypoglycemic mechanisms of components from Morus alba L.

Mechanism Component Reference
inhibition of α-glucosidase chalcomoracin Liu et al. (2022)
chlorogenic acid; rutin Hunyadi et al. (2012)
dihydromorin; kuwanon C; kuwanon G; moracin M; norartocarpetin Kwon et al. (2022)
kuwanon H Zhou et al. (2022b)
morin Przeor (2022)
morusin; morusinol Zhou et al. (2022b)
oxyresveratrol Kwon et al. (2022)
1-deoxynojirimycin Jan et al. (2022)
Enhancement of glucose uptake via in-sulin signaling pathway/AMP-activated protein kinase isoquercetin Lim et al. (2021)
Increase insulin secretion of pancreatic β-cells syringic acid Jan et al. (2022)
3.2 Antioxidant activity

Studies found that isoquercetin and 4-O-caffeoylquinic acid in Mori folium showed strong antioxidant activity, and the 50% radical-scavenging concentrations were 10.63 ± 0.96 μg/mL and 10.63 ± 0.96 μg/mL, respectively (Ganzon et al., 2018). The researchers comprehensively evaluated the antioxidant activities of bioactive components from M. alba L. in DPPH and ABTS radical scavenging assays, found that the acetone extract showed potential antioxidant activities with SC50 values of 242.33 ± 15.78 and 129.28 ± 10.53 μg/mL, respectively (Hsu et al., 2022). The antioxidant mechanisms of components from M. alba L. are summarized in Table 9.

Antioxidant mechanisms of components from Morus alba L.

Mechanism Component Reference
inhibition of ROS production astragalin; kaempferol; luteolin; quercetin; taxifolin Yu et al. (2021)
inhibition of soluble epoxide hydrolase aesculetin; moracin B; moracin J; moracin M; moracin M 3′-O-β-glucopyranoside; mulberroside F; scopoletin; scopoline Li et al. (2020)
scavenging or inhibiting the production of free radicals anthocyanins Suriyaprom et al. (2021)
caffeic acid; chlorogenic acid; ferulic acid; gallic acid; myricetin; naringenin; p-coumaric acid; rosmarinic acid; rutin; sinapinic acid Polumackanycz et al. (2021)
mulberroside A; oxyresveratrol Thomas et al. (2022)
protocatechuic acid; isoquercetin Leyva-Jimenez et al. (2020)
4-O-caffeoylquinic acid Ganzon et al. (2018)
3.3 Anti-inflammatory activity

Studies have demonstrated that M. alba L. and its active compounds could inhibit the inflammation by suppressing leukocyte chemotaxis, further data about the mechanism showed that oxyresveratrol in M. alba L. could inhibit the CXCR4-mediated leukocyte migration of the CXCR4 receptor by inactivating the MEK/ERK pathway (Chen et al., 2013). In addition, oxyresveratrol was alos reported favourable anti-inflammatory effect through the inhibitions of iNOS/NO production, synthesis of PGE2 and activation of NF-κB(Chung et al., 2003). The methanol extraction of mulberry bark showed that components named kuwanon T and sanggenon A in mulberry bark contribute to the anti-inflammatory activities on microglia (BV2) and macrophages (RAW264.7) by the inhibitions of productions of prostaglandin E2, interleukin-6 and tumour necrosis factor-α, and the stimulation of expression of cyclooxygenase-2 (Ko et al., 2021). The anti-inflammatory active ingredients in mulbery are displayed in Table 10.

Anti-inflammatory mechanisms of components from Morus alba L.

Mechanism Name Reference
inhibition the release of pro-inflammatory cytokines mulberroside A Shi et al. (2023)
protocatechuic acid; isoquercetin Leyva-Jimenez et al. (2020)
inhibiting MEK/ERK signaling in leukocyte migration oxyresveratrol Chen et al. (2013)
inhibition of NF-κB pathway activity morusin Jia et al. (2020)
moracin O; moracin P Hardianti et al. (2020)
neochlorogenic acid Gao et al. (2020a)
kuwanon T Ko et al. (2021)
sanggenon A
downregulating INOS expression astragalin; kaempferol; luteolin; quercetin; taxifolin Yu et al. (2021)
regulating Nrf2 signaling pathways neochlorogenic acid Gao et al. (2020b)
kuwanon T Ko et al. (2021)
sanggenon A
removal of excess reactive oxygen/nitrogen species or interaction with their interacting enzymes cudraflavone B; kuwanon E; 4′-O-methylkuwanon E Kollar et al. (2013)
selective inhibition of COX-2 activity kuwanon A Baek et al. (2021)
3.4 Anti-cancer activity

Moracin D was demonstrated that it could decrease cell proliferation and induce apoptosis in breast cancer cells by inhibiting the transduction pathway of Wnt3a/FOXM1/β-catenin signal and the activation of caspase and GSK3β(Hwang et al., 2018). Sanggenol L, another natural flavonoid compound in Mori cortex, could induce the apoptosis through inhibiting the PI3K/Akt/mTOR signaling pathway, and accelerate the cycle arrest of prostate cancer cells by activating the p53 protein (Won and Seo, 2020). In addition, sanggenol L could also reduce cytotoxicity and apoptosis in ovarian cancer cells through activating cysteine aspartase and inhibiting NF-κB (Ko et al., 2021). Moracin N was an active ingredient in Mori folium, which exhibit anti-lung cancer properties through apoptosis and autophagy (Gao C. et al., 2020). Morusin, which separate from Mori cortex, was demonstrated effective anticancer activity by inhibiting the vitality of prostate cancer cells with minimal impact on normal prostate epithelial cells, reducing STAT3 activity via the inhibition of phosphorylation, nuclear accumulation and DNA-binding activity. Moreover, morusin showed well downregulation effect on the expression of STAT1 target genes of Cyclin D2. Furthermore, morusin could also decrease the activity of STAT3 in inducing the apoptosis in prostate cancer cells (Lim et al., 2015). The anti-cancer components in M. alba L. and their mechanisms are summarized in Table 11.

Anticancer mechanisms of components from Morus alba L.

Mechanism Component Reference
inhibition of the Akt/mTOR signalling pathway morusin Wu et al. (2023)
activating AMP-activated protein kinase morusin Park and Park (2020)
reducing STAT3 activity morusin Cho et al. (2017)
regulating bax and survivin expression morusin Kang et al. (2017)
induces autophagy guangsangon E Shu et al. (2021)
moracin N Gao et al. (2020b)
regulation of autophagy protein ATG3L16-related RNA molecule expression cyanidin-3-glucoside Zabady et al. (2022)
activating protein and inhibiting of signaling sanggenol L Won and Seo (2020)
moracin D Hwang et al. (2018)
inhibition of HIF-1α in tumours and DLL4 activity in the endothelium steppogenin Cha et al. (2023)
targeting the KDM4B-MYC axis sanggenon C Tang et al. (2023)
induces CHK1 degradation through the ubiquitin-proteasome pathway morusinol Guo et al. (2023)
3.5 Other activities

Beside the aforementioned activities, the ingredients in the different parts from M. alba L. also exhibit other activities such as melanin inhibition effect, hair growth, etc. Up to now, multiple constituents including norluciferin, moracin B, moracin J, moracin M-3′-O-β-glucopyranoside and moracin M-6-O-β-D-glucopyranoside againsting melanin were separated from the ethanol extracts of M. alba L. These components have a significant dose-dependent inhibition of melanin production, effectively suppressed the activity of tyrosinase in B10-F1 cells induced by α-melanocyte stimulating hormone and exhibited inhibitory effects on the expression of associated proteins, such as microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-associated protein-1 (Li Y. et al., 2018). Mulberroside F in Mori folium exhibit inhibitory effect on melanin and through the inhibition of tyrosinase and the formation of melanin in melanin-A cells (Lee et al., 2002). Moreover, little Mori cortex extract showed the stimulating on hair growth, enhance the secretion of growth factors, facilitating the transition of hair follicles from the resting phase to the growth phase, activating β-linker proteins, which is essential for inducing the growth phase (Hyun et al., 2021). Other pharmacological activities and the related mechanisms are summarized in Table 12.

Other pharmacological effects and their mechanisms of components from Morus alba L.

Activity Mechanism Component Reference
antigout blocking the RAS signaling pathway lanosterol acetate Oh et al. (2021)
antiviral interference with cell damage caused by influenza virus infection gallic acid Kim and Chung (2018)
direct inhibition of influenza virus entry morin hydrate Hong et al. (2020)
inhibition of viral neuraminidase sanggenon C Langeder et al. (2023a)
inhibition of SARS-CoV-2 proteases sanggenon C; sanggenon G; sanggenon O Wasilewicz et al. (2023)
antiulcer inhibition the releasion of histamine quercetin Garg et al. (2022)
inhibition the formation of platelet-activating factor rutin Garg et al. (2022)
antidepressant interacts with the 5-hydroxytryptaminergic sanggenon G Lim et al. (2015)
antiplatelet inhibition of thromboxane release mulberroside C Kwon et al. (2021)
inhibition of platelet aggregation morusinol Lee et al. (2012)
anti-fatigue increased glucose phosphatase activity γ-aminobutyric Chen et al. (2016)
anti-melanogenic inhibition of tyrosinase activity kuwanon G; mulberrofuran G Koirala et al. (2018)
inhibition of S1P lyase activity mulberroside A; oxyresveratrol Zheng et al. (2023)
anti-obesity regulation of gut microbial communities and lipid indices arabinose; D-galactose; D-galacturonic acid; D-glucose; D-glucuronic acid; D-mannose Yang et al. (2022a)
fucose
L-rhamnose
anti-bacteria blocking the binding of [1–14C]acetate to Staphylococcus aureus membrane lipids chalcomoracin; moracin C Kim et al. (2012)
neuroprotection maintenance of mitochondrial membrane potential and mitochondrial function cyanidin-3-glucoside Bhuiyan et al. (2011)
promoted nuclear translocation of the mitophagy regulator TFEB and activated the AMPK-ULK1 pathway morin Wang et al. (2023c)
cardioprotection enhancement autophagy of hypoxia-induced sanggenon C Gu et al. (2017)
prevent hair loss increased secretion of angiogenic paracrine factors chlorogenic acid; umbelliferone Hyun et al. (2021)
anti-alzheimer’s disease reduction of intracellular amyloid-β oligomer-induced cytotoxicity anthocyanins Ochiishi et al. (2021)
against Benzo [a]pyrene in epidermal keratinocytes activation of Nrf2-mediated signaling/inhibition of aryl hydrocarbon receptor signaling maclurin Kim et al. (2021)
relieve fever inhibition of arachidonic acid metabolic pathway tryptophan Qu et al. (2019)
anti-hyperuricemia inhibition of xanthine oxidase activity, and downregulation expression of mURAT1, mGLUT9, and mABCG2 polydatin Ge et al. (2023)
4 Future perspective

In recent years, with the continuous advancement of modern science and technology, researchers conducted in-depth investigations of multifarious constituents and pharmacological activities of M. alba L., including Mori folium, Mori ramulus, Mori cortex and Mori fructus, making its high medicinal potential valuable in contemporary society. Until now, there were some reviews about the pharmacologic activities of M. alba L. (Hao et al., 2022), however, in view of the crucial connection between pharmacological actions and ingredients, the revelation of the overall constituents of M. alba L. was extremely important. When referred to constituents of M. alba L. concluded in this paper, the primary constituents were phenols, flavonoids, alkaloids, etc.. Summing up the pharmaceutical actions of M. alba L., hypoglycemic, antioxidant and anti-inflammatory were the common activities, and different constituents may owned similar effects. As is well konwn that, the connection between ingredients’s structure and pharmaceutical effects was extremely important. Take flavonoids ingredients, for example, the diversiform flavonoids in M. alba L. exhibited anti-inflammatory action. Popularly, the modifications could affect the mechanisms of inflammation, including glycosylation, hydroxylation, etc. (Chen et al., 2018). For example, both quercetin and its glycoside derivative quercetine-3-glucoside exhibit same anti-inflammatory activity with distinctive mechanisms of action. Quercetin downregulated the INOS expression (Leyva-Jimenez et al., 2020), however, isoquercetin inhibited the release of pro-inflammatory cytokines (Yu et al., 2021). Besides, different activities of constituents may owned the similar mechanisms. For example, AMP-activated protein kinase was related to both the anti-hpyerglycemic effect and anti-cancer action of M. alba L. Besides, when referred to the anti-oxidant and anti-inflammatory activities of M. alba L., the inhibition of soluble epoxide hydrolase was the same mechanism. These information indicated that one mechanism maybe related to diversified activities of M. alba L. based on the similar compounds. To sum up, the ingredients of M. alba L. were diverse, and the effect owned the characteristics of multiple approaches and multiple targets.

Nowadays, in order to extend the application of M. alba L. in TCM and food, the toxicity assessments of M. alba L. were evaluated by various experiments. When referred to Mori folium, the LD50 was higher than 15.0 g/kg bw in the acute toxicity test, indicating that Mori folium was deemed as safe and it may own a wide application as food or nutritional supplements (Li Y. et al., 2018). Besides, Mori fructus was a familiar edible food in daily life, and it was widely made into diverse foods such as fresh/dried fruit, fruit wine/juice, and other healthcare foods. From the sub-chronic oral toxicity test, the safe dose without observed adverse was up to 4200 mg/kg, meaning that Mori fructus was nontoxic under conventional edible dosage. Until now, there were none reports about the acute or chronic toxicity of the extracts of Mori cortex. However, the maximum tolerated dose of oral administration of the active ingredient named sanggenon C, an active ingredient derived from Mori cortex as well as identificated in Mori ramulus, was up to 100 mg/g (Langeder et al., 2023b). However, resveratrol, another active constituent in Mori cortex and Mori ramulus, was reported controversial toxicity, the metabolites of resveratrol may exhibit cytotoxic effects (Shaito et al., 2020), meaning that Mori cortex and Mori ramulus may owned a ralative reasonable safe space when applied. Hence, in order to improve the expansive value of M. alba L., the detailed illustrations of acute and long-term toxicity of Mori cortex and Mori ramulus were particularly vital in further studies for researchers.

 5 Conclusion

This review summarized the chemical profiles and the pharmacological activities of M. alba L., as well as the safety and the structure-activity relationship. Totally 198 of constituents including phenols, alkaloids, coumarins, carbohydrates, terpenoids, organic acids, anthocyanins, and other constituents were concluded. Among the chemical ingredients, 140 of them were phenols, indicating that phenols may played a critical role in this plant. Modern pharmacological research showed that M. alba L. exhibited hypoglycemic, antioxidant, anti-inflammatory, anti-cancer and other activities, illustrating that M. alba L. has showed favourable applications in pharmaceutical and food fields. Furhter biological activities and the related mechanisms of the ingredients in M. alba L. were needed in order to promote the development of pharmaceutical industry. In addition, more nutritional valve analysis and toxicity research data were particularly important for the development of M. alba L. in food scope.

 Author contributions

YW: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Resources, Supervision, Writing–original draft, Writing–review and editing. QA: Conceptualization, Data curation, Formal Analysis, Methodology, Resources, Supervision, Writing–original draft, Writing–review and editing. MG: Data curation, Formal Analysis, Investigation, Methodology, Resources, Supervision, Writing–review and editing. HG: Investigation, Resources, Supervision, Writing–review and editing. WY: Investigation, Resources, Supervision, Writing–review and editing. MZ: Data curation, Investigation, Supervision, Writing–review and editing. JM: Investigation, Methodology, Supervision, Writing–review and editing. ZL: Investigation, Resources, Writing–review and editing. QL: Conceptualization, Data curation, Formal Analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Writing–review and editing. JL: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing–review and editing.

 Funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The present study was supported by the Project from Qiqihar Academy of Medical Sciences (QMSI2023Z-16, 2021-ZDPY-011, QMSI2021M-12, and QMSI2021L16), Science and Technology Department of Heilongjiang Province (LH2023H100).

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

 Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2024.1364948/full#supplementary-material

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