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Journal of Herbal Medicine
Abstract Volume 24, December 2020, 100398 Generated by , an expert-curated
chemistry database.
Introduction

Section snippets
Promising anti-sickling and fetal
References (40)
hemoglobin inducing effects of Boerhavia
Cited by (2)
diffusa root extract on sickle cell
erythrocytes Recommended articles

Firdosh Shah a, Mitesh Dwivedi a , Chirag V. Parikh b Review on Trillium govanianum Wall. ex
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https://doi.org/10.1016/j.hermed.2020.100398 Get rights and content The effect of Aqueous, Ethanolic extracts
of Rheum ribeson insulin sensitivity,…
inflammation, oxidative
Journal of Herbal Medicine, stress
Volume 24,in patients
2020, Artic…
Abstract Atie
with Ghafouri,
type 2…, Farzad Shidfar
diabetes mellitus: A
Randomized, Double-Blind, Placebo-
Sickle cell disease (SCD) is a genetic blood disorder and currently available drugs
Ethnomedicinal
Controlled Trial knowledge of the Garo
are ineffective and come with numerous side effects B. diffusa has been reported as
community of two villages in western…
an important herb in the ayurvedic texts. Although studies have shown
Assam,ofIndia
Journal Herbal Medicine, Volume 20, 2020, Artic…
immunomodulatory and anti-inflammation activities, the anti-sickling activity and
Simi Talukdar, Abhik Gupta
fetal hemoglobin (HbF) inducing potential of Boerhavia diffusa have not yet been
explored. Therefore, the present study was aimed to assess anti-sickling and HbF Show 3 more articles
induction effects of B. diffusa aqueous root extract in sickle cell erythrocytes
obtained from SCD patients. The in vitro anti-sickling activity of the extract was
evaluated microscopically via the Emmel Test. The HbF inducing activity of the Article Metrics
extract was determined on SCD erythrocytes through HPLC. The different doses and
Citations
time-dependent treatments of the test extract and drug control (hydroxyurea)
suggested that 30 mg/mL extract for 60 min exerts significant anti-sickling effect on Citation Indexes: 2
SCD erythrocytes compared to the negative control (P < 0.0001). The anti-sickling
Captures
activity of test extract was comparable to hydroxyurea. Moreover, the test extract
showed significant increased HbF% in SCD patients’ erythrocytes at 30 mg/mL Readers: 22
concentration for 120 min compared to negative control (P < 0.0001). The test
extract showed similar HbF inducing potential when compared to hydroxyurea. In
View details
addition, the percentage of sickling was remarkably reduced with treatment of test
extract in both severe and less severe SCD groups compared to negative control. The
test extract and hydroxyurea were found to have similar anti-sickling effects
irrespective of the severity of the disease. Overall, these results show for the first
time the potent anti-sickling and HbF inducing activity of aqueous root extract of
Boerhaviadiffusa, which may be used as an herb-based alternative therapy in SCD
patients, warranting future in vivo studies.

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Introduction

Sickle cell disease (SCD) is a genetic condition which occurs due to a mutation at
the 6th position of the β-globin chain of hemoglobin. This devastating blood
disorder results in severe clinical complications such as vaso-occlusive crisis, acute
chest syndrome, hemolytic anemia, pulmonary hypertension, nephritic syndrome
and may also manifest into entire organ damage (Rees et al., 2010). It was estimated
that there were over 305,800 births with SCD across the globe with millions of
people presently affected worldwide (Piel et al., 2013) and India is the second worst
country to be affected with 42,016 predicted babies born with the highest βS allele
frequencies (Hockham et al., 2018). In India, among the 8.912 million tribal
population of Gujarat state, which includes Dhodia, Dubla, Kukna, Gavit, Varli,
Kokni and Kotwadia, seventy thousand individuals are expected to have SCD and at
least 0.9 million with Sickle Cell Trait (Sickle Cell Anemia Control Program, 2018.).
The survey of Indian Council of Medical Research (ICMR) during the year 2014, also
reported that about 30 % of children suffering from SCD die before they reach
adulthood (14 years of age), in the non-modernized tribes (Kolcha, Kotwadia &
Kathodi) of South Gujarat (Sickle Cell Anemia Control Program, 2018).

Though the treatment of sickle cell disease has increased considerably during the
past decades, the development of an effective treatment modality has been
hampered by several factors including difficulties in the optimal dose and schedule,
the methods of evaluation, and financial support. The percentage of patients who
benefit from bone marrow transplants and gene therapy interventions in SCD has
remained too small to justify the general use of such strategies. Moreover, the lack
of a suitable donor, cost of treatment and severe side effects are the main obstacles
in the path of such treatments for SCD. Hydroxyurea has been considered as an
ideal drug for the treatment of SCD, since it has provided therapeutic benefits for
reversing the sickle cell condition by inducing fetal hemoglobin (Agrawal et al.,
2014). Despite wide acceptance of hydroxyurea as an anti-sickling agent, one of the
major drawbacks is its moderate toxicity (beyond 30 mg/kg/day), especially when it
is administered for long term treatment (Kinney et al., 1999). Moreover, most of the
individuals in developing countries who have SCD belong to tribal groups which are
below the poverty line and cannot afford the high cost of treatment (Nikhar et al.,
2011). Therefore, there is a need for inexpensive, effective and safe therapeutic
alternative agents for SCD.

Over the past several decades, research has been ongoing to determine efficient
naturally occurring anti-sickling agents which could overcome the debilitating
effects of available drugs and the cost of managing the disease. This study is also an
attempt towards exploring such natural therapeutics for SCD. The plant Boerhavia
diffusa, commonly known as ‘red hogweed’, is included as a key ingredient in 35
different formulations in ayurvedic texts (Bhowmik et al., 2012). In Ayurveda, it is
considered a “Rasayana” herb which has been said to possess several medicinal
properties such as immunomodulation, anti-cancer, anti-inflammation, anti-aging,
anti-diabetic, cerebrally strengthening and hepatoprotection activities (Shikha et
al., 2014; Kaur, 2019; Oyebode et al., 2018; Akhter et al., 2019). However, its anti-
sickling activity has not been explored yet. Therefore, the present study was aimed
to evaluate the anti-sickling and HbF inducing activity of the aqueous root extract
of B. diffusa in the erythrocytes obtained from SCD patients including severe and
less severe disease groups.

Section snippets

Collection of plant & preparation of aqueous extract of B. diffusa

roots

The roots of B. diffusa were collected from the botanical garden of the Maliba
Pharmacy College, Uka Tarsadia University, Surat, Gujarat, India. The identification
was confirmed by the Dr. Bimal S. Desai, Assistant Professor of Botany, Department
of Basic Sciences, College of Forestry, ASPEE College of Horticulture and Forestry,
Navsari Agricultural University, Navsari, Gujarat, India. The specimen of B. diffusa
root was deposited (voucher no. SHAH/CGBIBT/02/18-19) in the herbarium of
ASPEE…

Evaluation of anti-sickling effect of the B. diffusa aqueous root

extract on sickle cell erythrocytes

A total of 16 samples of SCD patients were evaluated for anti-sickling activity of

aqueous extract of B. diffusa roots (test extract) on the basis of different doses of the
extract and different time duration. The demographic characteristics of SCD
patients are shown in Table 1.…

Discussion

The structural modification within the β-globin chain of haemoglobin results in the
formation of abnormal haemoglobin and leads to sickle-shaped RBCs. The plant-
derived anti-sickling agents may be considered as a crucial stepping-stone towards
improving the health of SCD patients. The plant-based anti-sickling agents act
through the inhibition of polymerization, reducing the oxidative damage or by
inducing increased HbF levels (Fig. 5). Previous studies have shown that certain
plants possess…

Conclusion

This study, showed for the first time that the root extract of B. diffusa may have
novel anti-sickling effects and HbF-inducing potential comparable to the standard
anti-sickling drug hydroxyurea on sickled erythrocytes under in vitro conditions. In
addition, the root extract was found to have potent anti-sickling effects on severe
SCD patients’ erythrocytes. Therefore, this investigation of B. diffusa root extract for
its anti-sickling and Hb- inducing activities may pave the way for the…

Funding

This work was supported by grant to MD {UTU/RPS/1268/2018–2019}, Uka Tarsadia

University (UTU), Bardoli, Gujarat, India.…

Ethical approval

All procedures performed in this study involving human participants were in

accordance with the ethical standards of the Institutional-Human Research Ethical
Committee (HREC), Maliba Pharmacy College, Uka Tarsadia University, Bardoli,
Gujarat, India and with the 1964 Helsinki declaration and its later amendments or
comparable ethical standards. All patients and healthy control subjects signed
informed consent.…

Informed consent

Informed consent was obtained from all individual participants included in the
study.…

CRediT authorship contribution statement

Firdosh Shah: Investigation, Methodology, Validation, Formal analysis, Writing-

Original draft preparation. Mitesh Dwivedi: Conceptualization, Funding acquisition,
Investigation, Methodology, Project administration, Resources, Supervision,
Visualization, Writing - reviewing & editing. Chirag V. Parikh: Investigation,
Methodology, Formal analysis, Data curation.…

Declaration of Competing Interest

The authors report no declarations of interest.…

Acknowledgments
We thank all Sickle cell disease patients and control subjects for their participation
in this study. We are thankful Dr. Piyush Shah, Chief District Medical Officer of
Surat and Dr. Naitik Chaudhary, Chief District Medical Officer of Tapi for providing
permission to collect patients’ blood samples. We also extend our big gratitude to
Dr. Harish Patel, General Physician, Bajipura, Mr. Akash Chaudhary and Ms.
Kajolpreet Kaur Mayall for supporting in blood collection. We are thankful to Uka…

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Hydroxyurea in sickle cell disease: drug review
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F. Akhter et al.
Therapeutic efficacy of Boerhaavia diffusa (Linn.) root methanolic extract
in attenuating streptozotocin-induced diabetes, diabetes-linked
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Biomed. Res. Ther. (2019)

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View more references

Cited by (2)

Anti sickling potential and chemical profiling of traditionally used

Woodfordia fruticosa (L.) Kurz leaves
2022, Arabian Journal of Chemistry

Citation Excerpt :
…These herbal drugs serve as agents that alter membrane stability, reduce hemolysis and
osmotic fragility, inhibit HbS polymerization, or reverse the RBC sickling (Nurain et al., 2017).
There has been an increased interest in determination of potent naturally occurring anti-
sickling agents which could overcome the debilitating effects of available drugs and the high
costs associated with the SCD management and treatment (Shah et al., 2020). In the current
study W. fruticosa, a traditionally used medicinal plant by the tribal communities of
Amarkantak region was evaluated for its anti-sickling, anti-inflammatory and anti-oxidant
potential.…

Show abstract

Revisiting fetal hemoglobin inducers in beta-hemoglobinopathies: a

review of natural products, conventional and combinatorial therapies
2022, Molecular Biology Reports

View full text

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