Review of Literature of Stephania glabra L

1. AJIT AVASTHI (2010) Research on antidepressants in India, Many studies have evaluated the
efficacy of antidepressants in depression and have shown that most of the currently
marketed antidepressants are useful. In addition, studies also suggest usefulness of
antidepressants in generalized anxiety disorder, dysthymia and common mental disorders.
Many of the recent studies have been of good design and have followed double blind
randomized controlled design and had reasonable sample size. Further, several studies have
been carried out at multiple sites throughout the country. The available data also suggest
that antidepressants are more cost-effective than other modalities of treatment for
depression. In addition, there is some evidence to suggest the usefulness of clomipramine in
OCD and that of fluoxetine in management of OC symptoms in schizophrenia. However,
some major limitations of the research have been that almost all the data available in
relation to treatment of depression pertains to acute phase treatment and rarely studies
have evaluated the continuation phase treatment. There is also lack of data with regard to
the efficacy and effectiveness in the maintenance phase treatment. Surprisingly, no study
has evaluated the efficacy/effectiveness of SSRIs in the management of OCD. There is a need
to conduct studies to evaluate the usefulness of antidepressants in the management of
panic disorder and depression in medically ill subjects. Studies are also required to evaluate
the efficacy of SSRIs in the management of OCD, and to study the usefulness of
polypharmacy in the management of depression and other disorders. Studies are few and
sparse and there is a need for multi-centric studies in such a vast country.
2. JOSINE E. VERHOEVEN (2023) Antidepressants or running therapy: Comparing effects on
mental and physical health in patients with depression and anxiety disorders, While the
interventions had comparable effects on mental health, running therapy outperformed
antidepressants on physical health, due to both larger improvements in the running therapy
group as well as larger deterioration in the antidepressant group.

3. NIRMAL RAJ MARASINE (2021) Use of Antidepressants among Patients Diagnosed with
Depression: A Scoping Review, Our study revealed that the majority of antidepressant users
were aged between 40 and 50 years, females, married, housewives, lower income, and
highly educated people. SSRIs were found to be highly prescribed over TCAs, SNRIs, MAOIs,
and atypical antidepressants. Among the prescribed SSRIs, sertraline was the dominant SSRI.
The result of this study suggests the further need for high-quality studies, which may
consider the use of data sources like clinical files and patient self-reports, and also includes
reports on whether antidepressants were prescribed to treat physical or mental symptoms.
4. MARK HAMER (2011) Antidepressant medication use and future risk of cardiovascular
disease: the Scottish Health Survey, Although replication is required, the increased risk of
CVD in men and women taking TCAs was not explained by existing mental illness, which
suggests that this medication is associated with an excess disease burden.
5. OMAR A. ALMOHAMMED (2022) Antidepressants and health-related quality of life (HRQoL)
for patients with depression: Analysis of the medical expenditure panel survey from the
United States, The real-world effect of using antidepressant medications does not continue
to improve patients’ HRQoL over time. Future studies should not only focus on the short-
term effect of pharmacotherapy, it should rather investigate the long-term impact of
pharmacological and non-pharmacological interventions on these patients’ HRQoL.
6. YUNXI ZHENG (2023) The application of antidepressant drugs in cancer treatment, This
review revealed that antidepressants have anticarcinogenic function which is associated
with different signaling pathways and changing of microenvironment. This study summarizes
the mechanism of cell apoptosis and tumor cell metabolism, which may be unique cancer
 therapeutic targets. In addition, ten kinds of antidepressants are introduced, including four
kinds of SSRIs, two kinds of TCAs, two kinds of NA/5-HT reuptake inhibitor, one kind of
tetracyclic antidepressants and one kind of MAOI. We mainly focus on the direct anticancer
effects of antidepressants, and secondary focus on the use of antidepressants as adjunctive
therapy in cancer treatment for the relief of psychotic disorders (e.g., depression, anxiety).
The Mechanism for antidepressants directly effects on tumor cells are involved in cell
apoptosis, antiproliferative effects, mitochondria-mediated oxidative stress, DNA damaging,
changing of immune response and inflammatory conditions, and acting by inhibit multidrug
resistance of cancer cells. Antidepressants are also used in combination therapy with typical
anti-tumor drugs which shows a synergic effect in anti-tumor. By contrast, the promotion
roles of antidepressants in increasing cancer recurrence risk, mortality, and morbidity are
also included. Further clinical experiments and mechanism analyses were required. The
precise mechanisms require additional investigation. We anticipate that a comprehensive
understanding of the process behind antidepressants-mediated anti-carcinogenic activities
will yield new insights for cancer prevention and clinical therapy.
7. RAHEEL I MEMON (2019) A Review of Novel Antidepressants: A Guide for Clinicians, The
multimodal mechanisms of actions of new antidepressants explain that depression may not
be caused by the simple deficit of serotonin, but rather can be related to “flooding”
5HT1A autoreceptors in midbrain peri-raphe areas by serotonin itself through the action of
glutamate, noradrenaline, and histamine. There is limited research on the use of the novel
antidepressants in human subjects, and further studies are warranted to reveal substantial
difference and other novel attributes of these new medications. The content published in
Cureus is the result of clinical experience and/or research by independent individuals
or organizations. Cureus is not responsible for the scientific accuracy or reliability of
data or conclusions published herein. All content published within Cureus is intended
only for educational, research and reference purposes. Additionally, articles
published within Cureus should not be deemed a suitable substitute for the advice of
a qualified health care professional. Do not disregard or avoid professional medical
advice due to content published within Cureus.
8. SUJITA W. NARAYAN (2024) Efficacy and safety of antidepressants for pain in older adults: A
systematic review and meta-analysis, For most chronic painful conditions, the benefits and
harms of antidepressant medicines are unclear. This evidence is predominantly from trials
with sample sizes of 100, have disclosed industry ties and classified as having unclear or high
risk of bias.
9. LAYLA BLEIBEL (2025) Unveiling the Anti-Inflammatory Effects of Antidepressants: A
Systematic Review of Human Studies over the Last Decade, The relationship between
inflammation and depression is complex and remains an area of active investigation. Despite
the numerous variables in the studies presented in this review, which are discussed in the
limitations section, and the application of strict inclusion and exclusion criteria, it seems
likely that there is a link between antidepressants and their anti-inflammatory effects. Levels
of pro-inflammatory factors were mostly found to be decreased with treatment with SSRIs
(escitalopram, fluoxetine, sertraline, paroxetine, and fluvoxamine), SNRIs (venlafaxine),
esketamine, and ketamine. Additionally, the anti-inflammatory cytokine IL-10 was found to
be increased upon treatment with fluoxetine, paroxetine, and esketamine, and IL-4 was
increased upon treatment with fluoxetine. However, it should be emphasized that there are
studies showing effects different from those described, which means that in this conclusion,
we are only pointing out certain patterns and associations between antidepressant drug
classes and changes in cytokine levels. This presents a new potential for investigating the
pathophysiology of depression as it presents more evidence of its relationship with
inflammation and how the treatment of inflammation could decrease depressive symptoms.
Such findings can also provide insight into new therapeutic approaches for MDD. Further
 research is necessary to gain a more comprehensive understanding of the relationship
between antidepressant therapy, inflammatory pathways, and treatment outcomes in
depression. Long-term and larger-scale studies are needed to determine whether current
findings reflect only acute effects or are sustained over time, and to evaluate the
reproducibility and broader physiological impact of antidepressants. Additionally, (i)
randomized controlled trials (RCTs) stratified by demographic factors such as age and gender
are necessary to determine how these variables influence the inflammatory response and
therapeutic outcomes. Incorporating pre-treatment and post-treatment inflammatory
biomarker profiling would help elucidate differential responses across subgroups. Moreover,
(ii) studies investigating specific molecular markers within inflammatory pathways, such as
NF-κB and the NLRP3 inflammasome, may help identify predictors of therapeutic efficacy.
Finally, given the limited existing evidence, (iii) further clinical trials exploring the anti-
inflammatory and antidepressant effects of novel agents such as esketamine are also
warranted.
10. OLE KÖHLER-FORSBERG (2023) Efficacy and Safety of Antidepressants in Patients With
Comorbid Depression and Medical Diseases, Despite the paucity of large and well-conducted
RCTs studying antidepressants for comorbid depression in medical diseases, this umbrella
systematic review and meta-analysis demonstrates that antidepressants are efficacious and
safe for comorbid depression in medical diseases, with effect sizes that are similar to those
reported for antidepressants in MDD without medical comorbidity. Furthermore,
antidepressants can prevent the development of depression in some medical diseases, but
this finding should be weighed against potential adverse effects. It is important to screen for
and manage comorbid depression in patients with medical diseases, and clinicians should
choose treatments based on patient preferences and the antidepressant’s risk-benefit ratio.
Future large, high-quality RCTs should include head-to-head comparisons between
antidepressants to expand the knowledge on potential differences in efficacy and safety
between antidepressants for depression comorbid with medical diseases and to allow more
specific treatment recommendations for distinct medical diseases.
11. SHWETA M. NAWGHARE (2024) Pharmacological Evaluation of Amaranthus viridis Linn
leaves Extract for Anti Alzheimer’s Activity in Rat Models, The pharmacological evaluation of
Amaranthus viridis Linn plant extract for its anti-Alzheimer’s activity presents promising
findings indicative of its potential therapeutic efficacy. Through a combination of behavioral
assessments using rat models like the Morris Water Maze and Elevated Plus Maze, along
with biochemical analyses focusing on parameters such as brain acetylcholine activity, the
study provides compelling evidence of the extract’s neuroprotective and cognitive-
enhancing properties. Results demonstrate significant improvements in spatial learning,
memory retention, and reduced anxiety-like behavior in rats treated with the MEAV 200
mg/kg, MEAV 400 mg/kg extract and donepezil when compared to negative control group.
Moreover, the observed increase in brain acetylcholine activity suggests that the extract
may modulate cholinergic neurotransmission, a critical pathway implicated in Alzheimer’s
pathology. These findings underscore the potential of Amaranthus viridis Linn extract as a
novel therapeutic agent for Alzheimer’s disease, warranting further investigation into its
specific mechanisms of action and clinical [Link], this study contributes valuable
insights into the search for alternative treatments for Alzheimer’s disease and highlights the
importance of exploring natural compounds with neuroprotective properties in combating
this debilitating condition.
12. MD. TANVIR KABIR (2021) Anti-Alzheimer’s Molecules Derived from Marine Life:
Understanding Molecular Mechanisms and Therapeutic Potential, There is a substantial
need for safe, effective, and novel treatments for AD. Natural products derived from marine
organisms have the potential to serve as an excellent source that can be used to expand the
pharmaceutical pipeline. Various novel compounds derived from marine organisms have
 exhibited significant effects in several in vivo and in vitro studies against AD pathogenesis.
Research shows that nature is a great source of compounds that can be used for AD
treatment. It is now feasible to develop effective bioactive compounds from marine sources
because of the technological advances made in harvesting samples and because of advances
in the purification and characterization of the products. Therefore, more studies are
required on marine organisms to develop novel and effective therapeutic agents to treat AD.
13. LI-KAI HUANG (2023) Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update,
Successful phase 3 trials such as Clarity AD (lecanemab) and EMERGE (aducanumab) have
evaluated anti-amyloid treatment in mild AD (Fig. 2). Trials that do not target specific
pathophysiologies are becoming fewer in all phases (Figs. 2 and 3). However, an increasing
number of early-phase trials of therapies for symptoms, including cognitive enhancers and
agents for relieving BPSD, are being conducted. This reflects the unmet clinical need for such
therapies (Figs. 2 and 3). Similarly, an increasing number of phase 1 trials involving DMTs,
particularly those targeting both anti-amyloid and anti-tau mechanisms, has been noted,
indicating the importance of basic research (Fig. 3). Outcome measurement tools have also
become more diverse, which has enabled meaningful improvements in AD and the efficacy
of treatments to be clearly determined in clinical trials. Overall, the field of AD clinical trials
is evolving, and additional promising treatments for AD are likely to be developed in
the near future.
14. RENHUI DAI (2022) Anti-Alzheimer's disease potential of traditional chinese medicinal herbs
as inhibitors of BACE1 and AChE enzymes, As far as the current situation is concerned, many
studies have shown that some naturally occurring compounds can simultaneously inhibit the
dual targets of BACE1 and AChE. This provides a new idea for us to develop anti-AD
inhibitors. In the follow-up work, researchers can use the structures of these compounds to
construct pharmacophore models based on the dual-target inhibitory activity of these
compounds, and use the constructed models to identify key chemical features of dual-target
inhibitors of AChE and BACE1. Through cost analysis, Fischer random verification and other
methods to find the optimal pharmacophore model, and then screening in various large
databases, more inhibitors with excellent inhibitory activity can be found.A major shift from
a monotherapy approach to an integrative, individualized, multi-therapeutic approach,
especially for chronic and complex diseases such as Alzheimer's disease, may be effective. In
recent years, screening active ingredients with AD chemoprophylaxis from traditional
Chinese medicine has become one of the important directions of AD research, especially
since the various universities and research institutes in the United States have carried the
research project of "natural inhibitors of AD", a large number of researchers have screened
natural active substances. With the deepening of the research on natural products, boffins
also realized that the therapeutic effect of screened single-target inhibitors was far less than
expected, so the research focuses gradually shifted to developing dual-target inhibitors. This
article discusses compounds that simultaneously inhibit both targets BACE1 and AChE,
hoping to help develop dual-target inhibitors against AD. In this paper, the experimental and
research progress of various compounds contained in natural traditional Chinese herbal
medicines in treating AD was reviewed in detail, and a database of natural small molecule
inhibitors of AChE and BACE1 was constructed. These works provide new research ideas for
the comprehensive development and application of traditional Chinese medicine, and
provide a theoretical basis for preparing low-toxicity and high-efficiency anti-AD inhibitors,
which have certain industry promotion value.
15. ABDALLAH E ABDALLAH (2024) Review on anti-alzheimer drug development: approaches,
challenges and perspectives, Herein, AD potential therapeutic targets have been discussed,
along with the clinically studied relevant drugs. As can be seen above, only a few drugs have
been approved for the treatment of AD. Galantamine, donepezil, and rivastigmine (ChEIs),
memantine (NMDA antagonist), and aducanumab and lecanemab (selective anti-Aβ
 monoclonal antibodies) are the currently approved drugs. This limited number of clinically
used drugs against AD does not reflect the large number of proteins and enzymes identified
as significant therapeutic targets of AD or the extensive number of drugs studied in the
clinical trials of AD. But this image reflects the complexity of the disease and the lack of
concrete evidence for the exact, definite cause of the disease. Accordingly, AD can be
considered a multifactorial disease that requires a deeper understanding of its etiology to
give priority to the most crucial targets. At the same time, early diagnosis of the disease is of
great importance to maximize the benefits of the treatment; especially, it was found that
amyloid plaques and neurofibrillary tangles can be detected decades before the appearance
of symptoms.274 As we saw earlier, lecanemab has been approved for the early stages of
AD. So, the identification of early detectable biomarkers of AD is highly significant.
Furthermore, there is some evidence that the approach to prevent further formation of
amyloid plaques is not enough for the treatment of AD in the sense that the
neurodegeneration is triggered by the neurotoxic effects of the already aggregated Aβ. This
may provide an explanation for the failure of almost all clinical trials based on the
prevention of Aβ aggregation. So, all aspects should be taken into account in any further
clinical study. The clinical data given in this work reveals GSM and QC inhibitors as the most
promising classes involving inhibition of the formation of toxic Aβ. Additionally, α-secretase
activators enhance proteolysis of APP in the non-amyloidogenic pathway. At the same time,
the current study presented many therapeutic classes that have been proven to protect
neurons from the toxic effects of Aβ. They include the neuroprotective GABAA agonists,
antioxidants, anti-inflammatory, and immunomodulatory. Furthermore, the significant
effects of PP2A activators and GSK-3β inhibitors in preventing neurofibrillary tangles should
also be considered. For future work, it may be beneficial in such a case to apply molecular
hybridization in order to develop potential drugs that work on more than one target linked
firmly to AD. Otherwise, a combination of AD drugs is highly recommended. Clinical trials of
drugs acting on Aβ and tau protein in combination with neuroprotective agents may change
the current situation and reveal a significant protocol for AD treatment. For the design of
new anti-alzheimer small molecules, two isosteric nuclei showed very significant therapeutic
properties, including reduction of the production of further toxic Aβ, activation of the
cleavage of APP to soluble Aβ rather than the insoluble one, neuroprotection against the
toxic effects of accumulated Aβ, and symptomatic improvement in cognitive functions.
These two promising isosteric nuclei are benzimidazole and pyrazolopyridine. We saw above
that their derivatives revealed QC inhibition, α-secretase activation, GABAA modulation, and
5HT antagonist activity, showing very promising clinical results. The importance of these
nuclei was highlighted by the therapeutic effects of their isostere, xanthine nucleus. We
found that xanthine derivatives exhibited PDE inhibition as well as antioxidant activity. The
most significant of them is benzimidazole in the sense that imidazole is considered a zinc
binding group in QC inhibition, and on it a class of anti-alzheimer drugs were built. This class
is called non-NSAID-derived imidazole GSMs, as explained earlier. Accordingly, these nuclei
can be used as a scaffold for building new candidates for potential multi-target anti-
alzheimer activity, taking together the clinical results and molecular structure of their
derivatives discussed in the current study.
16. A. Y. KIM (2024) Alzheimer’s disease and its treatment–yesterday, today, and tomorrow, In
conclusion, recognizing that there are multiple contributory factors including familial and life
style that can result in the development of AD a “one-size fits all” approach to treatment is
inappropriate and in addition to an early recognition and reduction of modifiable risk factors
that would also help reduce systemic inflammation, new drug targets need to be explored
and studied with a particular focus on early-stage intervention and metabolic contributions
(Chakrabarti et al., 2015). Drug development, plus early detection and intervention, will be
facilitated if biomarker testing for AD from blood tests can be validated. Besides p-tau
 (Ashton et al., 2024) other proteins including GFAP, neurofilament light (Nfl), growth
differentiation factor-15, and latent-transforming growth factor beta-binding protein 2, have
been reported to be potential blood bio-markers for AD (Guo et al., 2024; Qiang et al.,
2024). Advances in pre-clinical models of AD are also required. Animal models, notably with
rodents, have been the mainstay for drug testing and a large number of transgenic mouse
models are available; however, there are significant limitations to the data obtained from
the study of small animals (McKean et al., 2021). An ex vivo model that captures all of the
features of the human pathology is required and an important advance was made when a
human brain 3D organoid was generated using induced pluripotent stem cells (iPSCs) from
subjects with AD (Raja et al., 2016). The use of 3D human stem cell models of AD should
greatly facilitate drug discovery and development (Arber et al., 2017; Centeno et al., 2018).
17. PRASANTH NV (2024) Evaluation of In Vivo Anti Alzheimer's Activity of Vigna radiata and
Vigna pilosa using Beta Amyloid Induced Neurotoxicity in Rats, From the results it can be
concluded that the treatment with ethyl acetate extract of Vigna radiata and ethanolic
extract Vigna pilosa could ameliorate the effect of Aβ (1-42) on cognitive functions,
attenuated oxidative stress and neuroinflammation in rats. The study demands further
extensive research to develop potential therapeutic agents from these plants for the
management of AD.
18. HUSSAIN T. BAKHSH (2024) Anti-Alzheimer potential of Solanum lycopersicum seeds: in
vitro, in vivo, metabolomic, and computational investigations, In this study, SLSE showed
neuroprotective, antiapoptotic, and anti-amnesic effects against brain damage and cognitive
decline brought on by AlCl3. The anti-AChE and antioxidant activities of SLSE may be
responsible for this effect. Using LC–HRESIMS, thirty-three compounds were dereplicated.
Furthermore, the bioinformatics study discovered 378 targets related to the major identified
compounds, of which only 133 were related to Alzheimer's and memory disorders, with APP,
AChE, and PSEN2 targets identified as the top genes. Gene enrichment analysis identified the
TRAIL signalling pathway and the glypican pathway as the biological pathways enriched by all
the gene sets under investigation. This study suggests the use of SLSE as a promising
therapeutic approach in the management of AD disease. To verify the findings, future
detailed mechanistic studies and secondary metabolites quantification in the extract are still
required to confirm the results.
19. NIHITHA SANKA (2019) An updated review on Anti-Alzheimer’s herbal drugs, Due to poor
patient compliance towards drugs and their lethal side effects upon choric usage, at
present there was a paradigm shift of patient choice of medication towards herbal
which made a revolution this due to many advantages over the medications it has less
adverse effects and they target the site easily upon slight modification its physicochemical
properties, in spite of all these herbal therapy is economical to all classes of population.
Even on any slight overdose of medicine will not be a problem. Out of all these
advantageous aspects herbal medicine became a best choice of medication for
management AD along with this regular meditation and yoga add more benefits for
better and fast recovery of patient from AD.
20. CHRISTOPHER H. VAN DYCK (2022) Lecanemab in Early Alzheimer’s Disease, Lecanemab
reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less
decline on measures of cognition and function than placebo at 18 months but was
associated with adverse events. Longer trials are warranted to determine the efficacy and
safety of lecanemab in early Alzheimer’s disease. (Funded by Eisai and Biogen; Clarity AD
[Link] number Current therapeutic agents for Alzheimer’s disease–related
dementia temporarily improve symptoms but do not alter the underlying disease course.1,2
Some evidence suggests that amyloid removal slows the progression of disease.3 One anti-
amyloid antibody (aducanumab) has received accelerated approval from the Food and Drug
[Link] is a humanized monoclonal antibody that binds with high affinity
to soluble amyloid-beta (Aβ) protofibrils, which have been shown to be more toxic to
neurons than monomers or insoluble fibrils.4-14 A phase 2b, dose-finding trial involving 854
participants with early Alzheimer’s disease did not show a significant difference between
lecanemab and placebo in a Bayesian analysis of 12-month change in a composite score
(primary end point). However, analyses at 18 months showed dose- and time-dependent
clearance of amyloid with lecanemab, and the drug was associated with less clinical decline
on some measures than placebo. In that trial, intravenous administration of 10 mg of
lecanemab per kilogram of body weight every 2 weeks was identified as an appropriate
dose, with a 9.9% incidence (<3% symptomatic) of amyloid-related imaging abnormalities
(ARIA) with edema or effusions (ARIA-E).15 We conducted a phase 3 trial (Clarity AD) to
determine the safety and efficacy of lecanemab in participants with early
Alzheimer’s disease.