Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Curr Pharm Biotechnol. 2024 Nov 1. doi: 10.2174/0113892010332012241027022502. 
Online ahead of print.

Biochemical Screening, In-vitro and In-silico Characterization of Citrullus 
colocynthis Fruit Extracts: A Combined Experimental and Computation Study.

Shehzadi SA(1), Ashraf MA(1), Shafiq N(2), Rida F(2), Javed A(3), Younas F(1), 
Un-Nisa W(4), Younus W(5).

Author information:
(1)Sulaiman Bin Abdullah Aba Al-Khail-Centre for Interdisciplinary Research in 
Basic Sciences (SA-CIRBS), International Islamic University-44000 Islamabad, 
Pakistan.
(2)Synthetic and Natural Product Drug Discovery Laboratory, Department of 
Chemistry, Government College Women University Faisalabad-38000, Pakistan.
(3)Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of 
Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
(4)International Islamic University, Islamabad Sulaiman Bin Abdullah Aba 
Al-Khail-Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS) 
Islamabad Pakistan.
(5)Department of Computer Science, Hamdard University, Islamabad, Pakistan.

BACKGROUND: Several medicinal plants are identified as therapeutic agents for 
the world's most deadly disease cancer. A member of the "Cucurbitaceae" family 
of medicinal plants, Citrullus colocynthis (C. colocynthis) has various 
pharmacological actions.
AIMS AND OBJECTIVES: In the present study we have focused on the phytochemical 
analysis, antimicrobial, anticancer and in silico investigation of fruit 
extracts of C. colocynthis. The chloroform, pure ethanolic and aq. ethanolic 
extracts of C. colocynthis whole fruit, peel and pulp separately have been 
investigated.
METHODS: The phytochemical analysis revealed the presence of alkaloids, 
flavonoids, steroids, phenols, saponins and glycosides in various parts of the 
fruit. Some compounds have been identified using GC-MS analysis by comparing 
with NIST library data. The antimicrobial activity of all extracts was checked 
by agar well diffusion method against five different bacterial strains such as 
A. baumannii, K. pneumonia, S. aureus, P. aeruginosa and E. coli. The zone of 
inhibition (ZOI) ranged between 11 mm to 27 mm against different strains.
RESULTS: The polar solvent extracts (ethanolic and aq. ethanolic extract) of 
peel showed good sensitivity against all bacterial strains as compared to 
non-polar solvent (chloroform extract), which showed activity only against 
Staphylococcus aureus and Pseudomonas aeruginosa. The cytotoxic activity of C. 
colocynthis all extracts against human brain cancer cell lines (U-87) was 
assessed using MTT assay.
CONCLUSION: The % cell viability of ethanolic (ET-PL), and aq. ethanolic extract 
of whole fruit and pulp showed promising results. The cancerous cell line U-87 
seems to be more sensitive towards polar solvents (ethanolic and aq. ethanolic) 
pulp extracts than peel. Further, based on invitro results, compounds identified 
in ET-PP were screened for their potential as antibacterial and anticancer 
agents through molecular docking and MMGBSA studies. These studies strongly 
supported the in-vitro study results and identified new drug candidates.

Copyright© Bentham Science Publishers; For any queries, please email at 
epub@benthamscience.net.

DOI: 10.2174/0113892010332012241027022502
PMID: 39492776


2. Reprod Toxicol. 2024 Oct 26:108737. doi: 10.1016/j.reprotox.2024.108737.
Online  ahead of print.

Shatavarin-IV rescues the Di (2-ethylhexyl) phthalate (DEHP) induced oxidative 
stress in rat granulosa cells in vitro.

Pandey V(1), Sharma A(2), Upadhayay S(1), Patel Y(1), Chauhan JK(2), Ayesha 
S(2), Sahu AN(3), Gupta R(4), Tripathi A(5), Dubey PK(6).

Author information:
(1)Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, 
Varanasi-221005, India.
(2)Department of Zoology, MMV- Banaras Hindu University, Varanasi-221005, India.
(3)Department of Pharmaceutical Engineering & Technology, IIT (BHU), Banaras 
Hindu University, Varanasi-221005, India.
(4)Department of Shalya chikitsa, Faculty of Ayurveda, IMS, Banaras Hindu 
University, Varanasi-221005, India.
(5)Department of Zoology, MMV- Banaras Hindu University, Varanasi-221005, India. 
Electronic address: animatripathi@bhu.ac.in.
(6)Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, 
Varanasi-221005, India. Electronic address: pkdubey@bhu.ac.in.

Studies provide notable evidence that oxidative stress (OS) mediated reactive 
oxygen species (ROS) disturb reproductive health. We have shown in our previous 
publication that exposure of Di-(2-ethylhexyl) phthalate (DEHP), induces OS 
mediated ROS generation which inhibits steroid synthesis. In the present study, 
we demonstrated the ameliorative/protective effects of one of the steroidal 
saponins, i.e., Shatavarin-IV, isolated from the roots of Asparagus racemosus 
against DEHP induced OS in rat granulosa cells. Granulosa cells were exposed 
with DEHP alone (400μM), Shatavarin-IV alone (8μg/ml), and a combination of DEHP 
+ Shatavarin-IV (400μM + 8μg/ml) in vitro for 24 hrs. Intracellular ROS, 
OS/hypoxia, mitochondrial membrane potential, steroid-responsive genes 
expression were analyzed. The results revealed that the effective dose of DEHP 
(400µg) significantly increased OS compared to the control by increasing ROS 
levels, mitochondrial membrane potential, and β-galactosidase activity with a 
higher level of apoptotic genes (Bax, Caspase-3) expression at mRNA level. 
Further, DEHP significantly (p<0.05) reduced mRNA expression of steroidogenic 
responsive genes (StAR, CYP17A1 and CYP19A1) in granulosa cells treated with 
above combination compared to control. Interestingly, co-treatment of DEHP + 
Shatavarin-IV significantly suppressed the DEHP induced OS, ROS, β-galactosidase 
levels and enhanced steroidogeneic and apoptotic gene expression activities, 
which suggests that Shatavarin-IV rescued DEHP-induced changes that may useful 
for the prevention of DEHP- induced reproductive toxicity.

Copyright © 2024. Published by Elsevier Inc.

DOI: 10.1016/j.reprotox.2024.108737
PMID: 39490591

Conflict of interest statement: Declaration of Competing Interest The authors 
declare the following financial interests/personal relationships which may be 
considered as potential competing interests Pawan K. Dubey reports 
administrative support, equipment, drugs, or supplies, and statistical analysis 
were provided by Banaras Hindu University. Pawan K. Dubey reports a relationship 
with Banaras Hindu University that includes: employment. Pawan K. Dubey has 
patent pending to Assignee. NA Conflict of Interest The authors declare that 
they have no known competing financial interests or personal relationships that 
could have appeared to influence the work reported in this paper.


3. Integr Cancer Ther. 2024 Jan-Dec;23:15347354241293790. doi: 
10.1177/15347354241293790.

Evaluation of the Efficacy, Safety, and Clinical Outcomes of Ginsenosides as 
Adjuvant Therapy in Hepatocellular Carcinoma: A Meta-Analysis and Systematic 
Review.

Zhang R(1), Liao Y(2), Gao Y(1), Tian H(1), Wu S(1), Zeng Q(1), He Q(1), Zhang 
R(1), Wei C(3), Liu J(1).

Author information:
(1)The First Department of Surgery, Shenzhen Traditional Chinese Medicine 
Hospital/The fourth Clinical Medical College of Guangzhou University of Chinese 
Medicine, Futian District, Shenzhen, Guangdong, China.
(2)The Fourth Clinical Medical College of Guangzhou University of Chinese 
Medicine, Futian District, Shenzhen, Guangdong, China.
(3)Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The 
Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, 
Shenzhen, Guangdong Province, China.

Background: Ginsenosides (GS), including total GS, Rh2, Rg3 and compound K (CK), 
have been utilized as adjuvants in transarterial chemoembolization (TACE), 
surgery, and chemotherapy for hepatocellular carcinoma (HCC) therapy. However, 
the safety and efficacy of such combination treatments have been contradictory 
across different studies. This study aims to systematically evaluate the 
efficacy and safety of GS as adjuvant therapy for HCC. Methods: A literature 
search of PubMed, CNKI, Wanfang Data, Cochrane Library, Embase, and Web of 
Science was conducted up to May 2024 for clinical randomized controlled trials 
(RCTs) on GS-based adjuvant treatments for HCC. Two researchers independently 
screened the literature, extracted relevant data, and assessed study quality. 
Meta-analysis was conducted using RevMan 5.4. Results: Nineteen articles 
involving 1448 patients were included. Meta-analysis showed that GS as an 
adjuvant therapy for HCC improved disease control rate (risk ratio (RR) = 1.42, 
95% CI [1.26, 1.60]), objective response rate (RR = 1.20, 95% CI [1.09, 1.32]), 
life quality (RR = 1.49, 95% CI [1.23, 1.79]), 1-year overall survival rate 
(RR = 1.27, 95% CI [1.06, 1.52]), 2-year overall survival rate (RR = 1.43, 
95% CI [1.06, 1.95]), ehanced Child-Pugh in A level (RR = 1.59, 95% CI [1.08, 
2.34]), Child-Pugh in B level (RR = 1.28, 95% CI [1.08, 1.52]); increased CD3+ 
(MD = 8.81, 95% CI [3.91, 13.71]), NKC (MD = 8.00, 95% CI [6.76, 9.24]) and CD4+ 
(MD = 9.38, 95% CI [8.04, 10.72]), and reduced incidence of adverse reactions 
including nausea and vomiting (RR = 0.66, 95% CI [0.57, 0.77]), anorexia 
(RR = 0.33, 95% CI [0.21, 0.50]), leukopenia (RR = 0.55, 95% CI [0.46, 0.67]) 
and myelosuppression (RR = 0.54, 95% CI [0.40, 0.74]); decreased Child-Pugh in C 
level (RR = 0.43, 95% CI [0.27, 0.68]) and CD4+/CD8+ ratio (MD = 0.50, 95% CI 
[0.47, 0.57]). Conclusions: In summary, GS combined with Western medical 
approaches (TACE, surgery, chemotherapy) for the treatment of HCC can improve 
clinical efficacy, increase overall survival rates, enhance patient life 
quality, and reduce the occurrence of adverse reactions. However, due to the 
generally low quality of the included studies, more large-sample, multi-center, 
high-quality, RCTs are warranted to further consolidate these findings.

DOI: 10.1177/15347354241293790
PMCID: PMC11526256
PMID: 39474841 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Conflicting InterestsThe 
author(s) declared no potential conflicts of interest with respect to the 
research, authorship, and/or publication of this article.


4. Biomolecules. 2024 Oct 4;14(10):1257. doi: 10.3390/biom14101257.

Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome 
Activation.

Hwang S(1)(2), Park MS(1)(2), Koo AJ(3), Yoo E(4), Song SH(1), Kim HK(1)(2), 
Park MH(1)(2), Kang JS(1)(2).

Author information:
(1)College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, 
Republic of Korea.
(2)Brain Busan 21 Plus Research Project Group, Kyungsung University, Busan 
48434, Republic of Korea.
(3)College of Engineering, North Carolina A&T State University, Greensboro, NC 
27411, USA.
(4)Chemical, Biological, and Bioengineering Department, North Carolina A&T State 
University, Greensboro, NC 27411, USA.

Platelets are essential blood components that maintain hemostasis, prevent 
excessive bleeding, and facilitate wound healing. Reduced platelet counts are 
implicated in various diseases, including leukemia, hepatitis, cancer, and 
Alzheimer's disease. Enhancing megakaryocytic differentiation is a promising 
strategy to increase platelet production. Compound K (CK), a major bioactive 
metabolite of ginsenosides from Panax ginseng, has demonstrated anti-cancer and 
neuroprotective properties. In this study, we investigated the effects of CK on 
megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) 
cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA 
expression of key megakaryocytic differentiation markers, including CD61, CD41, 
and CD42a, and promoted the formation of large, multinucleated cells in K562 
cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced 
apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 
cells. RT2 Profiler PCR array analysis further identified a marked increase in 
the expression of genes associated with the activation of the NLRP3 inflammasome 
in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that 
CK promotes megakaryocytic differentiation and apoptosis through the activation 
of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK 
may enhance platelet production, indicating its potential as a therapeutic 
candidate for platelet-related disorders and other associated diseases.

DOI: 10.3390/biom14101257
PMCID: PMC11506438
PMID: 39456190 [Indexed for MEDLINE]

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


5. Curr Top Med Chem. 2024 Oct 22. doi: 10.2174/0115680266315197241015101801. 
Online ahead of print.

Potential Anti-tumor Effects and Apoptosis-Inducing Mechanisms of Saponins: A 
Review.

Santos EEP(1), Andrade MLO(1), Nascimento IJDS(1), Cibulski SP(1), Alves HDS(1).

Author information:
(1)Programa de Pós-Graduação em Ciências Farmacêuticas. Universidade Estadual da 
Paraíba. Rua Baraúnas, 351, Bairro Universitário 58429-500 Campina Grande-PB, 
Brasil.

The search for effective cancer therapies highlights saponins, natural 
plant-derived compounds, as promising anticancer agents. These compounds induce 
apoptosis in cancer cells by activating caspases, essential enzymes for cell 
death. For example, Soyasapogenol B from Glycine max and Astragaloside IV from 
Astragalus membranaceus effectively trigger apoptosis in cancer cells. 
Additionally, saponins, such as Compound K from American ginseng and 
Saikosaponin from Bupleurum falcatum, affect extrinsic and intrinsic pathways, 
including mitochondrial release of cytochrome C and activation of caspase-9. 
Ziyuglycoside II also acts on both pathways and activates the ROS/JNK pathway. 
Understanding these mechanisms provides promising prospects for developing more 
specific and safer anticancer therapies. The review utilized the ScienceDirect, 
PubMed, and Google Scholar databases. It was found that original articles and 
reviews from journals indexed in these sources emphasized the antitumor 
capabilities of saponins and discussed their role in apoptosis induction and 
caspase activation. The activation of caspases by saponins in the apoptotic 
pathway involves two main pathways: the extrinsic pathway is initiated by 
external signals that activate caspase-8, while the intrinsic pathway starts 
with internal stimuli, causing the release of cytochrome c and the activation of 
caspase-9. These pathways both lead to the activation of effector caspases 
(caspases 3, 6, and 7), culminating in apoptosis, an essential process for 
maintaining cellular balance and eliminating damaged cells. Identifying saponins 
in the context of cancer and their mechanisms of action is an ever-evolving 
field. Future research may lead to more targeted and personalized therapies, 
highlighting the collaboration between basic and clinical research in this 
promising area of medicine.

Copyright© Bentham Science Publishers; For any queries, please email at 
epub@benthamscience.net.

DOI: 10.2174/0115680266315197241015101801
PMID: 39440734