Metabolomic Diversity and Spatial Localization of Bioactive Compounds in Hemp Achenes from Diverse Landraces

Jun Li; Sijia Wang; Huihua Wan; Ruikun He; Zhen Li; Ruofan An; Zhongbao Yue; Yaolei Mi; Weiqiang Chen; Xue Cao; Sifan Wang; Zhichao Xu; Lingjuan Zhu; Wei Ma; Shilin Chen; Wei Sun; Wei Yang

doi:10.1016/j.jpha.2025.101545

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2026 > Accepted Manu

Jun Li, Sijia Wang, Huihua Wan, Ruikun He, Zhen Li, Ruofan An, Zhongbao Yue, Yaolei Mi, Weiqiang Chen, Xue Cao, Sifan Wang, Zhichao Xu, Lingjuan Zhu, Wei Ma, Shilin Chen, Wei Sun, Wei Yang. Metabolomic Diversity and Spatial Localization of Bioactive Compounds in Hemp Achenes from Diverse Landraces[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101545

Citation:

Jun Li, Sijia Wang, Huihua Wan, Ruikun He, Zhen Li, Ruofan An, Zhongbao Yue, Yaolei Mi, Weiqiang Chen, Xue Cao, Sifan Wang, Zhichao Xu, Lingjuan Zhu, Wei Ma, Shilin Chen, Wei Sun, Wei Yang. Metabolomic Diversity and Spatial Localization of Bioactive Compounds in Hemp Achenes from Diverse Landraces[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101545

Citation:

Jun Li, Sijia Wang, Huihua Wan, Ruikun He, Zhen Li, Ruofan An, Zhongbao Yue, Yaolei Mi, Weiqiang Chen, Xue Cao, Sifan Wang, Zhichao Xu, Lingjuan Zhu, Wei Ma, Shilin Chen, Wei Sun, Wei Yang. Metabolomic Diversity and Spatial Localization of Bioactive Compounds in Hemp Achenes from Diverse Landraces[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101545

PDF( 4462 KB)

Metabolomic Diversity and Spatial Localization of Bioactive Compounds in Hemp Achenes from Diverse Landraces

doi: 10.1016/j.jpha.2025.101545

Jun Li^a,b,
Sijia Wang^c,
Huihua Wan^a,b,
Ruikun He^d,
Zhen Li^a,e,
Ruofan An^a,b,
Zhongbao Yue^d,
Yaolei Mi^a,b,f,
Weiqiang Chen^a,b,
Xue Cao^a,b,
Sifan Wang^a,b,
Zhichao Xu^f,
Lingjuan Zhu^g,
Wei Ma^c,
Shilin Chen^b,h,
Wei Sun^{a,b
,
,},
Wei Yang^{a,b
,
,}

a. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China;
b. Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China;
c. College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China;
d. BYHEALTH Institute of Nutrition and Health, Guangzhou, 510663, China;
e. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China;
f. College of Life Science, Northeast Forestry University, Harbin, 150040, China;
g. School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China;
h. Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

Funds:

This work was supported by the scientific and technological innovation project of the China Academy of Chinese Medical Sciences (Grant No.: CI2023E002], the National Natural Science Foundation of China (Grant Nos.: 82204579 and 32300319), and the Fundamental Research Funds for the Central public welfare research institutes (Grant No.: ZZ13-YQ-045). We are grateful for the instrument support provided by the large-scale instrument sharing platform of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences. We also thank Create (Beijing) Technology Co., Ltd. for supporting MALDI imaging.

Received Date: Jun. 05, 2025
Accepted Date: Dec. 31, 2025
Rev Recd Date: Dec. 31, 2025
Available Online: Jan. 04, 2026

Abstract

Abstract

ABSTRACT:
- Hemp achene,
- Metabolomics,
- UHPLC-MS/MS,
- MALDI-MSI,
- Cannabinoids

FullText(HTML)

References(49)

References

[1]	Z. Xie, Y. Mi, L. Kong, et al., Cannabis sativa: Origin and history, glandular trichome development, and cannabinoid biosynthesis, Hortic. Res. 10 (2023), uhad150.
[2]	B. Farinon, R. Molinari, L. Costantini, et al., The seed of industrial hemp (Cannabis sativa L.): Nutritional quality and potential Functionality for Human Health and Nutrition, Nutrients 12 (2020), 1935.
[3]	J.C. Callaway, Hempseed as a nutritional resource: An overview, Euphytica 140 (2004) 65-72.
[4]	Q. Ma, C. Wang, W.R. Sawadogo, et al., Herbal medicines for constipation and phytochemical comparison of active components, Am. J. Chin. Med. 50 (2022) 723-732.
[5]	J.K. Kim, H. Y. Heo, S. Park, et al., Characterization of phenethyl cinnamamide compounds from hemp seed and determination of their melanogenesis inhibitory activity, ACS Omega 6 (2021) 31945-31954.
[6]	J.I. Alonso-Esteban, J. Pinela, A. Ciric, et al., Chemical composition and biological activities of whole and dehulled hemp (Cannabis sativa L.) seeds, Food Chem. 374 (2022), 131754.
[7]	X. Sun, L. Zhou, Y. Wang, et al., Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer, J. Pharm. Anal. 13 (2023) 726-744.
[8]	W. Sun, Z. Xu, C. Song, et al., Herbgenomics: Decipher molecular genetics of medicinal plants, Innovation (Camb) 3 (2022), 100322.
[9]	Q. Yang, A.H. Zhang, J H. Miao, et al., Metabolomics biotechnology, applications, and future trends: A systematic review, RSC Adv. 9 (2019) 37245-37257.
[10]	Y. Yang, S. Wang, R. Bai, et al., Geographic variation in secondary metabolites contents and their relationship with soil mineral elements in Pleuropterus multiflorum Thunb. from different regions, Sci. Tradit. Chin. Med. 2 (2024) 214-223.
[11]	K. Ning, C. Hou, X. Wei, et al., Metabolomics analysis revealed the characteristic metabolites of hemp seeds varieties and metabolites responsible for antioxidant properties, Front. Plant. Sci. 13 (2022), 904163.
[12]	G.F. Padilla-Gonzalez, A. Rosselli, N.J. Sadgrove, et al., Mining the chemical diversity of the hemp seed (Cannabis sativa L.) metabolome: Discovery of a new molecular family widely distributed across hemp, Front. Plant Sci. 14 (2023), 1114398.
[13]	E. Jang, H. Kim, S. Jang, et al., Concentrations of THC, CBD, and CBN in commercial hemp seeds and hempseed oil sold in Korea, Forensic Sci. Int. 306 (2020), 110064.
[14]	K.T. Desta, O.S. Hur, S. Lee, et al., Origin and seed coat color differently affect the concentrations of metabolites and antioxidant activities in soybean (Glycine max (L.) Merrill) seeds, Food Chem. 381 (2022), 132249.
[15]	X. Guo, X. Wang, C. Tian, et al., Development of mass spectrometry imaging techniques and its latest applications, Talanta 264 (2023), 124721.
[16]	Y.H. Chan, K.C. Pathmasiri, D. Pierre-Jacques, et al., Gel-assisted mass spectrometry imaging enables sub-micrometer spatial lipidomics, Nat. Commun. 15 (2024), 5036.
[17]	B. Li, D.R. Bhandari, C. Janfelt, et al., Natural products in Glycyrrhiza glabra (licorice) rhizome imaged at the cellular level by atmospheric pressure matrix-assisted laser desorption/ionization tandem mass spectrometry imaging, Plant J. 80 (2014) 161-171.
[18]	B. Feng, J. Zhang, C. Chang, et al., Ambient mass spectrometry imaging: Plasma assisted laser desorption ionization mass spectrometry imaging and its applications, Anal. Chem. 86 (2014) 4164-4169.
[19]	B. Li, E.K. Neumann, J. Ge, et al., Interrogation of spatial metabolome of Ginkgo biloba with high-resolution matrix-assisted laser desorption/ionization and laser desorption/ionization mass spectrometry imaging, Plant Cell Environ. 41 (2018) 2693-2703.
[20]	T. Liu, P. Wang, Y. Chen, et al., LC-MS and MALDI-MSI-based metabolomic approaches provide insights into the spatial-temporal metabolite profiles of Tartary buckwheat achene development, Food Chem. 449 (2024), 139183.
[21]	M. Bourjot, A. Zedet, B. Demange, et al., In vitro mammalian arginase inhibitory and antioxidant effects of amide derivatives isolated from the hempseed cakes (Cannabis sativa), Planta Med. Int. Open 3 (2016) e64-e67.
[22]	E. Nigro, G. Crescente, M. Formato, et al., Hempseed lignanamides rich-fraction: Chemical investigation and cytotoxicity towards U-87 glioblastoma cells, Molecules 25 (2020), 1049.
[23]	X. Yan, J. Tang, C. dos Santos Passos, et al., Characterization of lignanamides from hemp (Cannabis sativa L.) seed and their antioxidant and acetylcholinesterase inhibitory activities, J Agric Food Chem. 63 (2015) 10611-10619.
[24]	G. Lesma, R. Consonni, V. Gambaro, et al., Cannabinoid-free Cannabis sativa L. grown in the Po valley: Evaluation of fatty acid profile, antioxidant capacity and metabolic content, Nat. Prod. Res. 28 (2014) 1801-1807.
[25]	A. Smeriglio, E.M. Galati, M.T. Monforte, et al., Polyphenolic compounds and antioxidant activity of cold-pressed seed oil from finola cultivar of Cannabis sativa L, Phytother. Res. 30 (2016) 1298-1307.
[26]	L.O. Hanus, S.M. Meyer, E. Munoz, et al., Phytocannabinoids: A unified critical inventory, Nat. Prod. Rep. 33 (2016) 1357-1392.
[27]	L. Vollner, D. Bieniek, F. Korte, Hashish. XX. Cannabidivarin, a new hashish constituent, Tetrahedron Lett (1969) 145-147.
[28]	R.A. de Zeeuw, T.B. Vree, D.D. Breimer, et al., Cannabivarichromene, a new cannabinoid with a propyl side chain in Cannabis, Experientia. 29 (1973) 260-261.
[29]	TB. Vree, DD. Breimer, CA. van Ginneken, et al., Identification in hashish of tetrahydrocannabinol, cannabidiol and cannabinol analogues with a methyl side-chain, J. Pharm. Pharmacol. 24 (1972) 7-12.
[30]	T.B. Vree, D.D. Breimer, C.A. van Ginneken, et al., Gas chromatography of cannabis constituents and their synthetic derivatives, J. Chromatogr. 74 (1972) 209-224.
[31]	F.W.H.M. Merkus, Cannabivarin and tetrahydrocannabivarin, two new constituents of hashish, Nature 232 (1971) 579-580.
[32]	S.A. Ahmed, S.A. Ross, D. Slade, et al., Minor oxygenated cannabinoids from high potency Cannabis sativa L, Phytochemistry 117 (2015) 194-199.
[33]	R. Mechoulam, Y. Gaoni, Hashish. IV. The isolation and structure of cannabinolic cannabidiolic and cannabigerolic acids, Tetrahedron 21 (1965) 1223-1229.
[34]	Y. Shoyama, T. Fujita, T. Yamauchi, et al., Cannabichromenic acid, a genuine substance of cannabichromene, Chem. Pharm. Bull. 16 (1968) 1157-1158.
[35]	A. Shani, R. Mechoulam, ChemInform Abstract: Cannabielsoic acids, isolation and synthesis by a novel oxidative cyclization, Chem. Inf. 1974. https://doi.org/10.1002/chin.197443438.
[36]	Y. Shoyama, T. Yamauchi, I. Nishioka, Cannabis. V. cannabigerolic acid monomethyl ether and cannabinolic acid, Chem. Pharm. Bull. 18 (1970) 1327-1332.
[37]	I. Tlak Gajger, S. Ahmad Dar, Plant allelochemicals as sources of insecticides, Insects 12 (2021), 189.
[38]	E.H. Kim, S.H. Kim, J.I. Chung, et al., Analysis of phenolic compounds and isoflavones in soybean seeds (Glycine max (L.) Merill) and sprouts grown under different conditions, Eur. Food Res. Technol. 222 (2006) 201-208.
[39]	S. Kreft, M. Knapp, I. Kreft, Extraction of rutin from buckwheat (Fagopyrum esculentum Moench) seeds and determination by capillary electrophoresis, J. Agric. Food Chem. 47 (1999) 4649-4652.
[40]	J.C. McMillen, J.A. Fincher, D.R. Klein, et al., Effect of MALDI matrices on lipid analyses of biological tissues using MALDI-2 postionization mass spectrometry, J. Mass Spectrom. 55 (2020), e4663.
[41]	Y. Deng, S. Lu, Biosynthesis and regulation of phenylpropanoids in plants, Crit. Rev. Plant Sci. 36 (2017) 257-290.
[42]	O.J. Olatunji, H. Chen, Y. Zhou, Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H2O2 induced cytotoxicity in PC12 cells by attenuating oxidative stress, Biomed. Pharmacother. 93 (2017) 895-902.
[43]	W. Liu, Y. Feng, S. Yu, et al., The flavonoid biosynthesis network in plants, Int. J. Mol. Sci. 22 (2021), 12824.
[44]	M. Tura, M. Mandrioli, E. Valli, et al., Quality indexes and composition of 13 commercial hemp seed oils, J. Food Compos. Anal. 117 (2023), 105112.
[45]	A.L.G. de Brito Siqueira, P.V.V. Cremasco, J.O. Bahu, et al., Phytocannabinoids: Pharmacological effects, biomedical applications, and worldwide prospection, J. Tradit. Complement. Med. 13 (2023) 575-587.
[46]	M.P. Coelho, P. Duarte, M. Calado, et al., The current role of cannabis and cannabinoids in health: A comprehensive review of their therapeutic potential, Life Sci. 329 (2023), 121838.
[47]	M. Camilleri, Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans, Neurogastroenterol. Motil. 30 (2018), e13370.
[48]	L.R. Gournay, M.L. Ferretti, S. Bilsky, et al., The effects of cannabidiol on worry and anxiety among high trait worriers: A double-blind, randomized placebo controlled trial, Psychopharmacology 240 (2023) 2147-2161.
[49]	R. Abu-Sawwa, B. Scutt, Y. Park, Emerging use of epidiolex (cannabidiol) in epilepsy, J. Pediatr. Pharmacol. Ther. 25 (2020) 485-499.