Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Ethnopharmacol. 2022 Jun 28;292:115215. doi: 10.1016/j.jep.2022.115215. Epub
 2022 Mar 23.

Ethnopharmacological impact of Melaleuca rugulosa (Link) Craven leaves extract 
on liver inflammation.

Elsayed HE(1), Ebrahim HY(2), Mady MS(2), Khattab MA(3), El-Sayed EK(4), 
Moharram FA(2).

Author information:
(1)Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Ein 
Helwan, Cairo, 11795, Egypt. Electronic address: 
heba_alsayed01@pharm.Helwan.edu.eg.
(2)Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Ein 
Helwan, Cairo, 11795, Egypt.
(3)Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo 
University, Giza, 12211, Egypt.
(4)Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
University, Ein Helwan, Cairo, 11795, Egypt.

ETHNOPHARMACOLOGICAL RELEVANCE: Melaleuca species have been used by many ethnic 
communities for the management and treatment of several ailments as hemorrhoids, 
cough, skin infections, rheumatism, sore throat, pain, inflammation, and 
digestive system malfunctions. However, the detailed mechanistic pharmacological 
effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver 
inflammation has not been yet addressed.
AIM OF THE STUDY: The present study aimed to evaluate the anti-inflammatory, 
antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M. 
rugulosa leaves in relevance to their flavonoid content using an appropriate in 
vivo model.
MATERIALS AND METHODS: The aqueous methanol extract of M. rugulosa leaves was 
administered to the rats at three non-toxic doses (250, 500, and 1000 mg/kg) for 
seven days prior to the initiation of liver-injury induced by paracetamol 
(3 g/kg). Liver enzymes including alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in serum 
samples. The oxidative stress markers including reduced glutathione (GSH), 
malondialdehyde (MDA), and nitric oxide (NO) levels as well as the inflammatory 
markers such as tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B 
(NF-κB), were assessed in liver homogenate. The results were supported by 
histopathological and immuno-histochemical studies. The phytochemical 
investigation of the flavonoid-rich fraction of the aqueous methanol extract was 
accomplished using different chromatographic and spectroscopic techniques.
RESULTS: The aqueous methanol extract of M. rugulosa leaves showed a powerful 
hepatoprotective activity evidenced by the significant reduction of MDA and NO 
levels, as well as increasing GSH and catalase activity. Moreover, the extract 
exhibited anti-inflammatory and antiapoptotic activities witnessed by decreasing 
TNF-α, NF-κB, iNOS, p-JNK, caspase-3, BAX, and increasing Bcl-2 levels. 
Moreover, the pretreatment of rats with all doses of M. rugulosa leaves extract 
showed a significant decrease in liver weight/body weight (LW/BW) ratio, and 
total bilirubin induced by paracetamol. On the other hand, the chromatographic 
separation of the flavonoid-rich fraction afforded twenty known flavonoids 
namely; iso-orientin (1), orientin (2), isovitexin (3), vitexin (4), 
quercetin-3-O-β-D-glucuronid methyl ether (5), 
quercetin-3-O-β-D-mannuronpyranoside (6), isoquercetin (7), quercitrin (8), 
kaempferol-3-O-β-D-mannuronopyranoside (9), kaempferol-7-O-methyl 
ether-3-O-β-D-glucopyranoside (10), guaijaverin (11), avicularin (12), 
kaempferide-3-O-β-D-glucopyranoside (13), astragalin (14), afzelin (15), 
luteolin (16), apigenin (17), quercetin (18), kaempferol (19), and catechin 
(20).
CONCLUSION: The aqueous methanol extract of M. rugulosa leaves showed potential 
hepatoprotective, antioxidant, and anti-inflammatory activities against 
paracetamol-induced liver inflammation which is correlated at least in part to 
its considerable phenolic content.

Copyright © 2022 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jep.2022.115215
PMID: 35337921 [Indexed for MEDLINE]


2. Zhongguo Zhong Yao Za Zhi. 2016 Jan;41(1):87-91. doi: 10.4268/cjcmm20160117.

[Flavonoid glycosides from callus cultures of Dysosma versipellis].

[Article in Chinese]

Chen RD(1), Duan RG(1)(2), Zou JH(1), Li JW(1), Liu XY(3)(4), Wang HY(3)(4), Li 
QH(2), Dai JG(1).

Author information:
(1)State Key Laboratory of Bioactive Substance and Function of Natural 
Medicines, Institute of Materia Medica, Peking Union Medical College & Chinese 
Academy of Medical Sciences, Beijing 100050, China.
(2)Institute of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 
150040, China.
(3)Tianjin Acelbio Co., Ltd., Tianjin 300457, China.
(4)Key Enterprise Laboratory for Large-Scale Medicinal Plant Cell Culture, 
Tianjin 300457, China.

Various chromatographic techniques, including silica gel column chromatography, 
Sephadex LH-20, preparative thin-layer chromatography, and preparative HPLC, 
were employed to isolate the chemical constituents from callus cultures of 
Dysosma versipellis. Structures of the compounds were elucidated based on UV, 
IR, MS and NMR spectroscopic data analysis. Totally, seven flavonoid glycosides 
were isolated from the 95% ethanol extract of the callus cultures and identified 
as kaempferol-3-O-[6″-(3″'-methoxy)-malonyl]-β-D-glucopyranoside(1), 
kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside(2), 
kaempferide-3-O-β-D-glucopyranoside(3), kaempferol-3-O-β-D-glucopyranoside(4), 
isoquercitrin(5), quercetin-4'-O-β-D-glucopyranoside(6) and 
kaempferol-3-(6″-malonyl)-β-D-glucopyranoside(7), respectively.All these 
compounds were isolated from callus cultures of D. versipellis for the first 
time.Compounds 1, 2, 3, 6 and 7 were firstly obtained from plant materials of D. 
versipellis, and compound 1 was a new compound.

Copyright© by the Chinese Pharmaceutical Association.

DOI: 10.4268/cjcmm20160117
PMID: 28845646 [Indexed for MEDLINE]

Conflict of interest statement: The authors of this article and the planning 
committee members and staff have no relevant financial relationships with 
commercial interests to disclose.


3. PLoS One. 2015 Jun 5;10(6):e0127441. doi: 10.1371/journal.pone.0127441. 
eCollection 2015.

Induction of Apoptosis in MCF-7 Cells via Oxidative Stress Generation, 
Mitochondria-Dependent and Caspase-Independent Pathway by Ethyl Acetate Extract 
of Dillenia suffruticosa and Its Chemical Profile.

Tor YS(1), Yazan LS(2), Foo JB(1), Wibowo A(1), Ismail N(1), Cheah YK(3), 
Abdullah R(4), Ismail M(1), Ismail IS(5), Yeap SK(6).

Author information:
(1)Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti 
Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
(2)Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti 
Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia; Department of Biomedical 
Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 
43400 UPM, Serdang, Selangor, Malaysia.
(3)Department of Biomedical Science, Faculty of Medicine and Health Sciences, 
Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
(4)Department of Veterinary Pathology and Microbiology, Faculty of Veterinary 
Medicine, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
(5)Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 
UPM, Serdang, Selangor, Malaysia.
(6)Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, 
Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.

Dillenia suffruticosa, which is locally known as Simpoh air, has been 
traditionally used to treat cancerous growth. The ethyl acetate extract of D. 
suffruticosa (EADs) has been shown to induce apoptosis in MCF-7 breast cancer 
cells in our previous study. The present study aimed to elucidate the molecular 
mechanisms involved in EADs-induced apoptosis and to identify the major 
compounds in the extract. EADs was found to promote oxidative stress in MCF-7 
cells that led to cell death because the pre-treatment with antioxidants 
α-tocopherol and ascorbic acid significantly reduced the cytotoxicity of the 
extract (P<0.05). DCFH-DA assay revealed that treatment with EADs attenuated the 
generation of intracellular ROS. Apoptosis induced by EADs was not inhibited by 
the use of caspase-inhibitor Z-VAD-FMK, suggesting that the cell death is 
caspase-independent. The use of JC-1 dye reflected that EADs caused disruption 
in the mitochondrial membrane potential. The related molecular pathways involved 
in EADs-induced apoptosis were determined by GeXP multiplex system and Western 
blot analysis. EADs is postulated to induce cell cycle arrest that is p53- and 
p21-dependent based on the upregulated expression of p53 and p21 (P<0.05). The 
expression of Bax was upregulated with downregulation of Bcl-2 following 
treatment with EADs. The elevated Bax/Bcl-2 ratio and the depolarization of 
mitochondrial membrane potential suggest that EADs-induced apoptosis is 
mitochondria-dependent. The expression of oxidative stress-related AKT, p-AKT, 
ERK, and p-ERK was downregulated with upregulation of JNK and p-JNK. The data 
indicate that induction of oxidative-stress related apoptosis by EADs was 
mediated by inhibition of AKT and ERK, and activation of JNK. The isolation of 
compounds in EADs was carried out using column chromatography and elucidated 
using the nuclear resonance magnetic analysis producing a total of six compounds 
including 3-epimaslinic acid, kaempferol, kaempferide, protocatechuic acid, 
gallic acid and β-sitosterol-3-O-β-D-glucopyranoside. The cytotoxicity of the 
isolated compounds was determined using MTT assay. Gallic acid was found to be 
most cytotoxic against MCF-7 cell line compared to others, with IC50 of 36 ± 1.7 
μg/mL (P<0.05). In summary, EADs generated oxidative stress, induced cell cycle 
arrest and apoptosis in MCF-7 cells by regulating numerous genes and proteins 
that are involved in the apoptotic signal transduction pathway. Therefore, EADs 
has the potential to be developed as an anti-cancer agent against breast cancer.

DOI: 10.1371/journal.pone.0127441
PMCID: PMC4457850
PMID: 26047480 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: The authors have declared 
that no competing interests exist.


4. Molecules. 2011 Dec 8;16(12):10214-26. doi: 10.3390/molecules161210214.

Antioxidant, anti-glycation and anti-inflammatory activities of phenolic 
constituents from Cordia sinensis.

Al-Musayeib N(1), Perveen S, Fatima I, Nasir M, Hussain A.

Author information:
(1)Department of Pharmacognosy, College of Pharmacy, King Saud University, 
Riyadh, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

Nine compounds have been isolated from the ethyl acetate soluble fraction of C. 
sinensis, namely protocatechuic acid (1), trans-caffeic acid (2), methyl 
rosmarinate (3), rosmarinic acid (4), kaempferide-3-O-β-D-glucopyranoside (5), 
kaempferol-3-O-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranoside (7), 
kaempferide-3-O-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside (8) and 
kaempferol-3-O-α-L-rhamno-pyranosyl (1→6)-β-D-glucopyranoside (9), all reported 
for the first time from this species. The structures of these compounds were 
deduced on the basis of spectroscopic studies, including 1D and 2D NMR 
techniques. Compounds 1-9 were investigated for biological activity and showed 
significant anti-inflammatory activity in the carrageen induced rat paw edema 
test. The antioxidant activities of isolated compounds 1-9 were evaluated by the 
DPPH radical scavenging test, and compounds 1, 2, 4 and 7-9 exhibited marked 
scavenging activity compared to the standard BHA. These compounds were further 
studied for their anti-glycation properties and some compounds showed 
significant anti-glycation inhibitory activity. The purity of compounds 2-5, 8 
and 9 was confirmed by HPLC. The implications of these results for the 
chemotaxonomic studies of the genus Cordia have also been discussed.

DOI: 10.3390/molecules161210214
PMCID: PMC6264710
PMID: 22158590 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.