Structurally Diverse Flavonolignans with Immunosuppressive and Neuroprotective Activities from the Fruits of Hippophae rhamnoides L.

Abstract

The fruit of Hippophae rhamnoides L. has been used for centuries in Europe and Asia as a food with high nutritional and medicinal values. In this study, a bioactivity-guided phytochemical investigation of H. rhamnoides L. has resulted in four new dimethylallylated flavonolignans (1–4), four new isopropylpentenone–flavonolignan heterodimers (5–8), two new geranylated flavonolignans (9 and 10), and 14 known flavonolignan derivatives (11–24); they were elucidated by their spectrometric and spectroscopic methods, including HR-ESI-MS, NMR, IR, and UV from the fruit of H. rhamnoides L. for the first time. Among them, compounds 2, 5, 6, 20, and 21 showed potent immunosuppressive activities with IC50 values from 19.42 ± 3.91 to 48.05 ± 12.56 μM. Meanwhile, compounds 1, 4, 11, 12, and 13 showed moderate neuroprotective activities, which increased the cell survival rate from 50.30 ± 4.24% for the model group to 71.63 ± 3.04%, 70.02 ± 4.13%, 61.53 ± 5.93%, 61.08 ± 3.58%, and 65.68 ± 4.88% at 10 μM, respectively. The hypothetical biogenetic pathway and preliminary structure–activity relationship were found and discussed scientifically.

Phytochemistry and pharmacology of sea buckthorn (Elaeagnus rhamnoides; syn. Hippophae rhamnoides): progress from 2010 to 2021

“…Other compounds, including 43 , 46 , 39 (ent-mururin A), 35 (mururin A), and 36 (mururin B) showed moderate neuroprotective activity. The compounds increased the survival rate of PC12 cells from 50.30% (negative control) to 61.08–71.63%, at 10 µM (Ma et al 2020 ). Water–methanol extracts from the fruit of different cultivars of SB exerted moderate anticholinergic activity, their IC 50 values ranged from 20.16 to 40.60 µg mL −1 ; the samples had also strong inhibitory activity against butylcholinesterase, with IC 50 < 0.01 µg mL −1 (Tkacz et al 2020 ).…”

“…Twenty four flavonolignans have been recently purified from the fruit of SB, including 10 new compounds, and 14 substances (Fig. 4 ) detected for the first time in this plant (Ma et al 2020 ). Known compounds included silychristin A ( 29 ), silychristin B ( 30 ), silybin B ( 31 ), silybin A ( 32 ), cinchonain Ia ( 33 ) cinchonain Ib ( 34 ), mururin A ( 35 ), mururin B ( 36 ), 5′-methoxyhydnocarpin D ( 37 ), 2,3-dehydrosilychristin ( 38 ), ent-mururin A ( 39 ), hydnocarpin D ( 40 ), ent-vaccinin A ( 41 ), and vaccinin A ( 42 ).…”

Chemophenetic Significance of Anomalocalyx uleanus Metabolites Are Revealed by Dereplication Using Molecular Networking Tools

“…Table 1. Compounds detected in the Anomalocalyx uleanus methanolic extracts by UPLC-Q-TOF-MS/MS (compounds 1-46) and gas chromatography-mass spectrometry (GC-MS) (47)(48)(49)(50). Level of confirmation: Level 1 (L1): structure confirmed by reference standard or structure elucidation by NMR spectroscopy, level 2a (L2a): probable structure by library spectrum match, and level 3 (L3): tentative candidates based on MS and MS 2 experimental data [18,19].…”

“…The families Euphorbiaceae and Meliaceae belong to the Rosids group; Meliaceae is included in the order Sapindales, while Euphorbiaceae is included in the order Malpighiales [46]. In addition to Meliaceae, cinchonain Ib (33) has already been identified in several families, such as Elaeagnaceae [47], Hypericaceae [48], Lauraceae [49], Rhizophoraceae [50], Rosaceae [51], Rubiaceae [52], Smilacaceae [53], and Theaceae [54] Chlorogenic acid (25) and its derivatives are present in Euphorbiaceae and could be isolated from some species of Euphorbiaceae, such as Jatropha aethiopica [55], Euphorbia peplus [56], Euphorbia hirta, Phyllanthus emblica, Ricinus communis [57], Sapium insigne [58], and Croton antisyphiliticus [39]. Coumarins are relatively common in many Euphorbiaceae genera, such as Pedilanthus [59], Cnidoscolus [22], Macaranga [60], Mallotus [61], Phyllanthus [62], Jatropha [63], Euphorbia [64], and others.…”

“…Column flow rate was 1 mL/min, equilibration time was 3.0 min, and helium was used as the carrier gas. The results were compared with the NIST library database, and it was possible to identify four esters (47)(48)(49)(50) [74].…”