Co esponding au ho : Ayush Agga wal
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E icacy and Sa e y o Rasayanam Gluco-Ca e in Adul s wi h Type 2 Diabe es Melli us:
A Randomized, Double-Blind, Placebo-Con olled Clinical S udy
Ayush Agga wal *
Rasayanam Nu ipha m P i a e Limi ed, Fla No. 697, Sec 69, IMT Fa idabad, Ha yana, India.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(01), 156-170
Publica ion his o y: Recei ed on 16 Augus 2025; e ised on 22 Sep embe 2025; accep ed on 24 Sep embe 2025
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.24.1.0853
Abs ac
Backg ound: Type 2 Diabe es Melli us is a ch onic me abolic condi ion ma ked by insulin esis ance and β-cell
impai men , esul ing in hype glycaemia and ela ed consequences. While pha maceu ical in e en ions a e s anda d,
he inc easing in e es in nu aceu icals has d i en esea ch in o he bal o mula ions.
Me hods: This was a p ospec i e, andomized, double-blind, placebo-con olled, wo-a m, pa allel-g oup, mul i-cen e
s udy conduc ed ac oss wo clinical si es in Pune, India. Fo y adul pa ien s (aged 18–70 yea s) wi h es ablished T2DM
on s able con en ional he apy we e g ouped andomly in a 1:1 a io o ecei e ei he Rasayanam Gluco-Ca e (30 ml
wice daily) o a placebo juice o 30 days. An al e a ion in glycosyla ed haemoglobin (HbA1c) be ween baseline o Day
30 was he p ima y endpoin . Seconda y endpoin s encompassed al e a ions in Quali y o Li e (QoL) assessed wi h he
QOLID22 ques ionnai e, sa e y assessmen s h ough ad e se e en (AE) moni o ing, and changes in haema ological
pa ame e s.
Resul s: All 40 andomized subjec s comple ed he s udy, wi h no p o ocol de ia ions a ec ing analysis. Baseline
demog aphics we e balanced be ween g oups wi h no s a is ically signi ican di e ences in age, gende , BMI, o clinical
his o y. The Rasayanam g oup demons a ed signi ican ly educed HbA1c le els compa ed o he placebo g oup. The
mean change in HbA1c om baseline o Day 30 was -1.04% in he Rasayanam g oup, compa ed o +0.08% in he placebo
g oup (p < 0.001). The leas squa es mean di e ence in HbA1c be ween g oups was -1.18% (95% CI: -1.44 o -0.92),
demons a ing s ong s a is ical and clinical ele ance. No signi ican ad e se e en s o ea men -eme gen ad e se
e en s (TEAEs) we e documen ed. The indings o his s udy can he e o e ac as a ca alys o inco po a ing p o en
Ayu edic o mula ions in o con en ional diabe es managemen , in acco dance wi h he WHO's global s a egy on
adi ional medicine.
Keywo ds: Type 2 Diabe es Melli us; Rasayanam Gluco-Ca e; Nu aceu icals; Hba1c; He bal Medicine
1. In oduc ion
Diabe es melli us (DM) is a non-in ec ious endoc ine diso de ma ked by imp ope ca bohyd a e me abolism and
hype glycemia esul ing om ei he de iciency o inadequacy o insulin. I esul s in p oblems including mic o ascula
(e.g., neph opa hy, e inopa hy) and mac o ascula diseases (e.g., co ona y hea disease, pe iphe al ascula disease).
The condi ion is ca ego ized in o wo ypes: (a) Type 1 DM (T1DM) which is insulin-dependen due o he des uc ion
o panc ea ic β-cells and (b) Type 2 DM (T2DM) which is non-insulin-dependen and is associa ed wi h insulin
esis ance and obesi y. Apa om his, Ges a ional DM which occu s du ing p egnancy, a ec s 2–4% o cases, usually
in he second o hi d imes e [1].
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As pe he In e na ional Diabe es Fede a ion (2016), 415 million people globally a e a ec ed, which is expec ed o ise
o 642 million by 2040. India, e med he "diabe es capi al o he wo ld", had 61.3 million diabe ics, and is expec ed o
double by 2030. U baniza ion, lack o physical ac i i y, s ess, poo die , malnu i ion, alcohol consump ion, and
in ec ions con ibu e o i s ise. The condi ion is mo e p e alen among women and less educa ed indi iduals,
pa icula ly in de eloping coun ies [2].
P ediabe es is a c ucial wa ning s age cha ac e ized by highe blood glucose le els ha do no ye mee he c i e ia o
T2DM. Wi hou in e en ion, many indi iduals wi h p ediabe es p og ess o ull-blown diabe es wi hin a ew yea s.
Diabe es is diagnosed using a ious blood suga es s including inge -p ick es , glucose ole ance es , as ing blood
suga es , and glycohemoglobin (HbA1c). No mally as ing glucose is a ound 80 mg/dL and pos p andial up o 160
mg/dL [3]. The e a e se e al ac o s which a ec diabe es, among hem oxida i e s ess plays an impo an ole in
diabe es pa hogenesis. I in ol es an imbalance be ween eac i e oxygen species (ROS) and an ioxidan s. These ROS
damage cells and issues, con ibu ing o a he oscle osis, β-cell dys unc ion, and complica ions. O he key molecula
pa hways in ol ed include he glucosamine pa hway, so bi ol pa hway, and p o ein kinase C s imula ion [4].
The g owing p e alence o T2DM and i s an eceden , p ediabe es, has in ensi ied he global sea ch o e ec i e and sa e
p e en i e s a egies. T1DM is managed wi h insulin, while Type 2 is ea ed wi h o al hypoglycemics like
sulphonylu eas, hiazolidinediones, and pep ide analogs [5]. Howe e , syn he ic d ugs o en ha e ad e se e ec s such
as nausea, omi ing, dysen e y, and anemia, he eby shi ing he end owa ds adi ional and ayu edic medica ions
o cu bing he cases o DM [6]. The WHO has iden i ied 21,000 plan s u ilized o medical uses globally, o which 2,500
species a e ound in India. App oxima ely 800 plan s ha e been documen ed o exhibi an idiabe ic p ope ies. A di e se
a ay o plan -de i ed ac i e molecules has demons a ed po en ial o applica ion in diabe es ea men [7]. Widely
used in Indian and Chinese adi ional medicine o hei minimal side e ec s, a o dabili y, and accessibili y, such
he bal app oaches include o mula ions like Rasayanam Gluco-Ca e (RGCa e), an Ayu edic polyhe bal blend known
o i s eju ena ing, an idiabe ic, an ioxidan , and adap ogenic p ope ies. I enhances me abolic heal h, suppo s
panc ea ic unc ion, and mi iga es oxida i e s ess and in lamma ion. The o mula ion con ains key ing edien s i.e.
Momo dica cha an ia (Ka ela) exhibi s signi ican an idiabe ic e ec s h ough a ious mechanisms such as insulin-
mime ic ac i i y, enhancemen o glucose up ake, s imula ion o insulin sec e ion, inhibi ion o gluconeogenesis, and
modula ion o key me abolic enzymes [8]. Eugenia jambolana (Jamun) con ains mal idin and e ulic acid [9]. I s ex ac
signi ican ly es o ed an ioxidan enzyme le els, including glu a hione pe oxidase, ca alase, glu a hione and supe oxide
dismu ase (SOD) by ee adical sca enging ac i i y and bioac i e phy ochemicals in he seed ke nel [10]. Gymnema
syl es e (Gudma ) p omo es β-cell egene a ion, supp esses o swee as e ecep o s, which educes suga c a ings
and s imula es insulin sec e ion [11]. Gymnemic acids, gu ma in, and gymnemasaponins we e highligh ed o hei
po en biological ac i i ies ela ed o glucose me abolism [12]. P e oca pus ma supium (Vijaysa ), a na u al analog o
es e a ol, known o enhance insulin sensi i i y and educe blood glucose le els [13-15]. Ma supsin and epica echin
demons a ed β-cell egene a i e p ope ies and imp o ed insulin sec e ion. Liqui i igenin and be be ine inhibi key
enzymes like α-glucosidase and aldose educ ase, educing pos p andial hype glycemia. O he componen s o he
RGCa e ha e Emblica o icinalis (Amla) which is ich in polyphenols and an ioxidan s [16]. I is ich in polyphenolics,
pa icula ly gallic acid, ellagic acid, and asco bic acid, which educes oxida i e s ess, a majo con ibu o o insulin
esis ance and β-cell dys unc ion, enhance insulin signalling pa hways, he eby imp o ing glucose up ake and imp o e
lipid me abolism, educing iglyce ides and low-densi y lipop o ein le els. Resea ch has also e ealed dec eased
as ing blood glucose and HOMA-IR sco es (Homeos a ic Model Assessmen o Insulin Resis ance), imp o ed se um
insulin le els and educed le els o malondialdehyde (MDA), a ma ke o lipid pe oxida ion - indica ing educed
oxida i e s ess [17]. T igonella oenum-g aecum (Fenug eek) delays suga abso p ion and enhances insulin elease [18-
20]. Diosgenin (a s e oidal saponin), la onoids, polyphenols, alkaloids (e.g., igonelline), galac omannans (soluble
ibe ) a e ecognized o hei hypoglycemic, insulin-sensi izing, and an ioxidan p ope ies [21]. Azadi ach a indica
(Neem) lowe s blood glucose and imp o es ci cula ion [22]. The sil e pa icles exhibi ed s ong inhibi o y e ec s on
α-glucosidase and α-amylase, enzymes c i ical o ca bohyd a e diges ion. The inhibi ion o hese diges i e enzymes
pos pones he abso p ion o glucose in he in es ine and helps in educing pos p andial hype glycemia, a key
he apeu ic a ge in T2DM [23]. Lage s oemia speciosa (Banaba) con ains co osolic acid wi h insulin-like e ec s [24,
25]. The NiO nanopa icles de eloped using Banaba demons a ed inhibi o y ac i i y agains α-glucosidase and α-
amylase enzymes. The esul s we e dose-dependen , wi h he NiO nanopa icles om Lage s oemia speciosa showing
he highes an idiabe ic po en ial. As diabe es is a g owing global conce n, especially in de eloping coun ies, he use o
adi ional he bal medicine o e s a sa e , holis ic al e na i e wi h minimal side e ec s, showing p omise in long- e m
diabe es managemen and p e en ion.
Howe e , mos o he he bal p oduc s a e in oduced in he ma ke based on empi ical knowledge a he han igo ous
scien i ic ials. Wi h India acing a g owing diabe ic popula ion and ising conce ns o e he ad e se e ec s o long-
e m use o syn he ic d ugs, such con olled ials a e essen ial. This gap be ween adi ional claims and clinical
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alida ion is a signi ican ba ie o in eg a ing nu aceu icals in o e idence-based heal hca e. The e o e, he RGCa e
s udy, designed as a p ospec i e, andomized, double-blind, placebo-con olled clinical ial add esses his gap by
e alua ing a well-es ablished he bal o mula ion h ough obus scien i ic me hodology. The e ec i eness o RGCa e
was compa ed o an iden ical placebo in educing HbA1c le els in adul s diagnosed wi h T2DM. The s udy no only
assesses he clinical e icacy in glycemic con ol bu also e alua es he b oade impac on quali y o li e o T2DM pa ien s
using he QOLID ques ionnai e a e ea men wi h RGCa e e sus placebo and de e mines he sa e y and ole abili y
o RGCa e based on ad e se e en epo ing and changes in labo a o y pa ame e s. I also esponds o he need o
holis ic, sa e , and cos -e ec i e op ions ha can complemen o subs i u e con en ional an idiabe ic he apies. These
objec i es a e di ec ly aligned wi h he esea ch gap by aiming o gene a e conc e e clinical e idence ha ei he
subs an ia es o challenges he he apeu ic claims o he bal an idiabe ic o mula ions h ough s a is ically alid,
e hically sound esea ch.
2. Ma e ials and Me hods
2.1. D ug de ails
2.1.1. S udy d ug (Rasayanam Gluco-Ca e Juice)
RGCa e (h ps:// asayanam.in/p oduc s/glucoca e-juice) is a polyhe bal o mula ion made up o s anda dized ex ac s
de i ed om eigh medicinal plan s adi ionally used in Ayu edic medicine o glycemic con ol and me abolic
suppo . The app oxima e o mula ion (pe 100 g) includes ex ac s de i ed om Jamun (Syzygium cumini) (15 %),
Ka ela (Momo dica cha an ia) (10 %), Gudma (Gymnema syl es e) (2.5 %), Vijaysa (P e oca pus ma supium) (2 %),
Me hi (T igonella oenum-g aecum) (2 %), Neem (Azadi ach a indica) (2 %), and Banaba (Lage s oemia speciosa L.)
(1.5 %) and Amla (Emblica o icinalis) juice (33 mL).
2.1.2. Compa a i e d ug - Placebo
The juice o mula ion consis s o 1 li e o demine alized wa e as he base, complemen ed by 0.5 ml o ca amel colo
o enhance isual appeal. Pec in (E440/INS 440) was used as a hickening agen (1 g) o imp o e ex u e and
consis ency. Ku ki (200 mg), known o i s dis inc bi e p o ile and po en ial hepa op o ec i e bene i s, was added o
impa a cha ac e is ic bi e as e. Addi ionally, 1 g o sal was inco po a ed o balance he o e all la o p o ile.
2.2. S udy design and plan
This s udy employed a p ospec i e, andomized, double-blind, placebo-con olled, wo-a m, pa allel-g oup design o
e alua e he e ec i eness and sa e y o RGCa e juice in people diagnosed wi h T2DM. The ial was conduc ed a wo
independen clinical si es. One was Sanjee an Hospi al F.P23, o Ka e Road, Kashibai Khila e Pa h, Opposi e Pune
Cen al, Pune, Maha ash a-411004 and second was D . Kinholka Speciali y Clinic B104, Bhamini a cade, nea PL
Deshpanse Ga den Sinhgad Pune, Opposi e Roshan K i ika socie y Pune, Maha ash a- 411030, India, adhe ing s ic ly
o he In e na ional Council o Ha monisa ion (ICH) Good Clinical P ac ice (GCP) no ms and Indian egula o y
amewo ks, including he New D ugs and Clinical T ial Rules.
2.3. S udy popula ion
A o al o 42 pa ien s we e sc eened, ou o which 40 eligible pa icipan s we e andomized in a 1:1 a io in o wo
g oups: one ecei ing he in es iga ional p oduc (RGCa e Juice) and he o he an iden ical placebo juice. The
andomiza ion p ocess was conduc ed using a p e-gene a ed code held secu ely o main ain he blinding o bo h
in es iga o s and pa icipan s h oughou he s udy. Each subjec was ins uc ed o consume 750 ml o he assigned
juice wice daily, wo hou s be o e b eak as and dinne , o a ea men du a ion o 30 days.
The inclusion c i e ia equi ed subjec s o be adul s (aged 18–70 yea s) wi h con i med T2DM diagnosis, who a e on
s anda d medica ion, capable o p o iding in o med consen in w i ing, complying wi h he in es iga ion's isi
schedule, ag ee o ake in es iga ional p oduc ill 30 h day, willing o ollow he p ocedu es as pe he s udy p o ocol
and ea men . Addi ionally, women o childbea ing po en ial we e equi ed o employ double-ba ie con acep ion
h oughou he s udy and mus p esen a nega i e p egnancy es p io o en ollmen . Subjec s we e excluded om he
s udy i hey had a his o y o insulin use o mo e han wo weeks wi hin wo mon hs p io o he sc eening isi ,
unde wen ba ia ic su ge y o any gas ic bypass, o planned o unde go such a p ocedu e du ing he s udy. Addi ional
exclusion c i e ia included a his o y o uns able angina, conges i e hea ailu e (CHF), pe iphe al a e ial
e en , ce eb o ascula acciden , ansien ischemic a ack, myoca dial in a c ion, o any e ascula iza ion p ocedu e
wi hin he six mon hs p eceding he sc eening isi , as well as planned ascula p ocedu es o su ge ies du ing he
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s udy pe iod. Fu he mo e, indi iduals wi h a his o y o cance o malignancy, p egnancy o b eas eeding, in en o
become p egnan du ing he s udy, known o suspec ed in ec ion wi h human immunode iciency i us, o any condi ion,
labo a o y abno mali y, o concomi an he apy ha , in he In es iga o 's opinion, could pose a isk o he subjec o
ende pa icipa ion con a y o he subjec 's bes in e es we e also excluded. The his o y o p esence o any medical
condi ions which impac s he quali y o li e, hype sensi i i y o p oduc o placebo, use o p esc ip ion medica ions
and/o non-p esc ip ion medica ions o weigh loss, cu en diagnosis o medical his o y o alcoholism and d ug
dependence, use o medica ions ha a e p ohibi ed wi h he he bal p oduc s as pe in es iga o disc e ion, any o he
condi ion which he p incipal in es iga o hinks may jeopa dize he sa e y o subjec s - pa ien s wi h uncon olled,
uns able como bidi ies and subjec s cu en ly en olled in o who ha e no comple ed a leas 30 days since concluding
ano he in es iga ional s udy o who a e ecei ing o he in es iga ional agen s a e also pe inen conside a ions. The
low cha o he s udy is ep esen ed in Figu e 1.
Figu e 1 S udy low cha
2.4. Clinical endpoin s and s a is ical app oach
Clinical assessmen s we e pe o med a baseline (Day 0) and a he end o he s udy (Day 30). The p ima y endpoin
was he change in HbA1c le els, while seconda y endpoin s included changes in quali y o li e assessed by he QOLID-
22 ques ionnai e, moni o ing o TEAEs, and changes in basic haema ological pa ame e s. Compliance was moni o ed
by acking he e u n o used in es iga ional p oduc bo les and pa ien dia ies. All sa e y and e icacy da a we e
analyzed s a is ically using Analysis o Co a iance (ANCOVA), and signi icance was de ined a p < 0.05. The s udy
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ensu ed 100% ea men compliance and epo ed no majo p o ocol de ia ions, wi hd awals, o ad e se sa e y
conce ns.
This igo ous and e hically s uc u ed me hodology aimed o p o ide obus clinical e idence o he e icacy and sa e y
o RGCa e, add essing he u gen need o alida ed he bal in e en ions in diabe es ca e.
2.5. Assessmen C i e ia
The assessmen c i e ia included a comp ehensi e e alua ion o demog aphic pa ame e s such as age, da e o bi h,
gende , ace, weigh , heigh , and Body Mass Index (BMI). A de ailed physical examina ion was conduc ed, encompassing
i al signs and sys emic e alua ions, including gene al appea ance, head and neck, ca dio ascula , espi a o y,
gas oin es inal, and ne ous sys ems, along wi h blood p essu e (B.P.), body empe a u e, and pulse a e
measu emen s. Clinical labo a o y in es iga ions comp ised hema ological es s, including ed blood cell (RBC) coun ,
whi e blood cell (WBC) coun , pla ele coun , hemoglobin concen a ion, and hema oc i le els. Fo women o
childbea ing age, a u ina y p egnancy es (UPT) was pe o med o ule ou p egnancy. Glycemic con ol was assessed
using HbA1c le els. Quali y o li e was e alua ed using he QOLID ques ionnai e. Addi ionally, any ad e se e en s and
p io medica ions, i applicable, we e eco ded h oughou he s udy du a ion.
3. Resul s and discussion
The e alua ion o RGCa e o he managemen T2DM p o ides compelling clinical e idence ega ding i s e icacy and
sa e y p o ile. The s udy ec ui ed 40 pa ien s, andomized in o wo equal g oups ecei ing ei he RGCa e Juice o a
placebo. The p ima y e icacy endpoin was he change in HbA1c, while seconda y endpoin s included changes in quali y
o li e (QOLID sco es) and sa e y ou comes.
3.1. Change in Glyca ed Haemoglobin (HbA1c) and QOLID assessmen
A baseline, he mean HbA1c le els we e 7.68 ± 1.55 % in he RGCa e g oup and 8.20 ± 1.89 % in he placebo (Figu e 2).
A e 30 days o in e en ion, he mean HbA1c le el in he ea men g oup signi ican ly dec eased o 6.64 ± 1.53 %,
while i sligh ly inc eased o 8.28 ± 1.61 % in he placebo g oup. The adjus ed leas squa es mean di e ence be ween
he g oups was -1.18 (SE = 0.126), wi h a p- alue o <0.001, indica ing signi ican di e ence (Table 1). This e lec s a
13.6 % educ ion in he ea men g oup compa ed o a ma ginal 1.0 % inc ease in he placebo g oup. This ou come is
signi ican as e en a 1% d op in HbA1c is associa ed wi h a 21% dec ease in diabe es- ela ed mo ali y and a 14%
decline in myoca dial in a c ions, as epo ed by he Uni ed Kingdom P ospec i e Diabe es S udy (UKPDS) [26].
Figu e 2 Mean HbA1c a baseline and Day 30 be ween RGCa e and Placebo
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The indings align wi h ea lie s udies examining he e ec s o he bal in e en ions on glycemic con ol. A s udy by
Baska an e al. [27] e alua ing Gymnema syl es e, one o he key ing edien s in RGCa e, epo ed a signi ican HbA1c
educ ion o e 10 mon hs in diabe ic pa ien s. Simila ly, Momo dica cha an ia (bi e melon) and P e oca pus
ma supium (Vijaysa ) ha e been shown o lowe blood glucose and imp o e insulin sensi i i y in p e ious ials [14,
27]. Compa able polyhe bal o mula ions o en epo educ ions be ween 0.5% and 1.0% o e longe pe iods, and a
ecen andomized con olled ial on a s anda dized mul i-he b o mula showed a signi ican bu smalle HbA1c
educ ion o e 90 days [28]. Howe e , wha se s he cu en s udy apa is he polyhe bal app oach, which in eg a es
he syne gis ic e ec s o mul iple adap ogenic he bs, he eby o e ing a b oade he apeu ic mechanism h ough
an ioxidan , an i-in lamma o y, and be a-cell egene a i e pa hways. The apid decline obse ed he e sugges s a
syne gis ic ac ion among he he bal componen s. In ensi e glycemic con ol, wi h educ ions o his magni ude, is well-
es ablished as a means o educe mic o ascula complica ions in T2DM pa ien s acco ding o la ge-scale s udies.
Mechanis ically, he e icacy may be a ibu ed o he complemen a y ac ions o ing edien s such as Momo dica
cha an ia (ac ing ia insulin-mime ic e ec s), Syzygium cumini (enhancing insulin sensi i i y and p o iding an ioxidan
ac i i y), Gymnema syl es e (s imula ing β-cell egene a ion), and o he s subs an ia ed in bo h expe imen al and
clinical esea ch [29].
Table 1 E ec o Rasayanam Gluco-Ca e e sus placebo on glyca ed hemoglobin (HbA1c) o e 30 days in adul s
RG Ca e (N = 20)
Placebo (N = 20)
Obse ed
Change om baseline
Obse ed
Change om baseline
Baseline
N
20
20
Mean
7.68
8.20
SD
1.522
1.889
Median
7.35
7.80
Min
5.30
5.90
Max
12.20
13.80
Day 30
N
20
20
20
20
Mean
6.64
-1.04
8.28
0.08
SD
1.527
0.448
1.607
0.425
Median
6.50
-1.10
8.00
0.05
Min
4.50
-2.10
6.00
-0.80
Max
11.50
-0.40
13.00
0.90
LS Mean (SE)
6.87 (0.089)
8.05 (0.089)
95% CI (LS Mean)
(6.69, 7.05)
(7.87, 8.23)
LS Mean Di e ence (SE)
-1.18 (0.126)
p- alue
<0.001*
95% CI (LS Mean Di )
(-1.44, -0.92)
Leas squa es mean, s anda d e o s, and con idence in e als come om analysis using an analysis o co a iance (ANCOVA) model wi h change in
HbA1c as he dependen a iable, ea men as ixed e ec and baseline sco e as a co a ia e.
*indica es signi ican esul
The seconda y ou come - quali y o li e, was measu ed using he alida ed QOLID ques ionnai e, and i imp o ed
signi ican ly in bo h g oups; howe e , he RGCa e exhibi ed a la ge gain han placebo (Figu e 3). A baseline, he mean
QOLID sco e in he Rasayanam g oup was 82.65, which ose o 93.70 a Day 30, ep esen ing a signi ican imp o emen
o 11.05 poin s (13.4%). In con as , he placebo g oup showed an inc ease om 83.65 o 92.20, o 8.55 poin s (10.2%).
Al hough bo h g oups exhibi ed imp o emen , likely due o gene al ial engagemen and suppo i e ca e, he ea men
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g oup’s supe io ou come was s a is ically signi ican (p = 0.036) (Table 2). This suppo s he hypo hesis ha RGCa e
no only aids in physiological glucose con ol bu also enhances pa ien s pe cei ed heal h and well-being. Imp o emen s
likely e lec no only be e me abolic s a us bu also mi iga ion o symp oma ic bu den and imp o ed o e all
wellbeing, ends obse ed in p io ials in ol ing in eg a i e o he bal diabe es in e en ions. Li e a u e inc easingly
ecognizes ha e en modes glycemic imp o emen s can ansla e o meaning ul QOL gains in people wi h ch onic
diabe es [29].
Figu e 3 Mean QOLID Assessmen Sco e change om baseline be ween RGCa e and Placebo
Table 2 Change in Quali y o Li e in Diabe es (QOLID-22) sco es o e 30 days in he Rasayanam Gluco-Ca e and placebo
g oups
RG Ca e (N = 20)
Placebo (N = 20)
Obse ed
Change om baseline
Obse ed
Change om baseline
Baseline
N
20
20
Mean
82.65
83.65
SD
5.860
5.779
Median
83.00
84.00
Min
70.00
73.00
Max
95.00
95.00
Day 30
N
20
20
20
20
Mean
93.70
11.05
92.20
8.55
SD
3.080
5.586
3.334
3.663
Median
93.50
11.50
93.50
9.00
Min
86.00
-1.00
86.00
2.00
Max
99.00
22.00
97.00
15.00
LS Mean (SE)
93.86 (0.591)
92.04 (0.591)
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95% CI (LS Mean)
(92.66, 95.06)
(90.84, 93.24)
LS Mean Di e ence (SE)
1.82 (0.837)
p- alue
0.036*
95% CI (LS Mean Di )
(0.13, 3.52)
Leas squa es mean, s anda d e o s, and con idence in e als come om analysis using an analysis o co a iance (ANCOVA) model wi h change in
QOLID Assessmen Sco e as he dependen a iable, ea men as ixed e ec and baseline sco e as a co a ia e.
*indica es signi ican esul
F om a pha macological s andpoin , RGCa e exhibi s mul idi ec ional an idiabe ic mechanisms including inhibi ion o
ca bohyd a e-me abolizing enzymes, egula ion o glucose homeos asis, imp o emen o mi ochond ial unc ion,
egene a ion o panc ea ic be a-cells, inhibi ion o glucose abso p ion in he in es ine and enhancemen o glucose
up ake in pe iphe al issues [30]. These mechanisms a e no specula i e; a he , hey a e suppo ed by bo h in i o and
in i o s udies o indi idual componen s, such as Gymnema syl es e [12, 29], Azadi ach a indica [31] and Emblica
o icinalis [32].
In his con ex , a ecen andomized, placebo-con olled, p oo -o -concep clinical s udy o e s aluable insigh s in o
how adi ional Ayu edic medicine can play a ole in cu bing his p og ession. The esea ch e alua ed he e icacy and
sa e y o Nisha-Amalaki capsules, a s anda dized Ayu edic o mula ion combining Cu cuma longa ( u me ic) and
Emblica o icinalis (amla), o p e en he ansi ion om p ediabe es o diabe es o e a six-mon h pe iod. Conduc ed on
62 p ediabe ic pa icipan s, he s udy was designed o compa e Nisha-Amalaki capsules wi h a placebo, while all
pa icipan s also ecei ed die a y and li es yle counseling. The p ima y goal was o assess changes in he Indian
Diabe es Risk Sco e, a alida ed sc eening ool ha includes bo h modi iable and non-modi iable isk ac o s. Seconda y
ou comes encompassed a ia ions in as ing and pos -glucose blood suga le els, HbA1c, insulin le els, insulin
esis ance (assessed using HOMA-IR), and indica o s o in lamma ion and oxida i e s ess. Addi ionally, he s udy
e alua ed adi ional Ayu edic symp om sco es and heal h- ela ed quali y o li e using he SF-36 ques ionnai e.
Pa icipan s who ecei ed Nisha-Amalaki showed ma ked imp o emen s in glycemic pa ame e s: as ing glucose, pos -
OGTT glucose, HbA1c, and insulin le els all declined meaning ully compa ed o baseline and o he placebo g oup.
Insulin sensi i i y imp o ed, as indica ed by a educ ion in HOMA-IR. Mo eo e , he e was a a o able modula ion o
oxida i e s ess ma ke s (dec eased MDA and inc eased SOD le els) and in lamma ion ( educed C- eac i e p o ein
le els). These biochemical changes sugges ha he o mula ion no only aided in glucose egula ion bu also add essed
unde lying me abolic dys unc ions associa ed wi h he p og ession o diabe es. Impo an ly, pa icipan s epo ed
imp o emen in Ayu edic symp oms associa ed wi h p ediabe es, such as excessi e hi s , u ina ion, a igue, and
bu ning sensa ions. Mo eo e , o he ea men g oup, quali y o li e imp o ed signi ican ly, pa icula ly in aspec s
ela ed o ene gy le els, emo ional well-being, and gene al heal h, especially in egions whe e Ayu eda is cul u ally
oo ed and heal hca e esou ces a e limi ed, such o mula ions could be ins umen al in educing he bu den o diabe es
[33].
A ecen placebo-con olled clinical s udy e alua ed he impac o daily supplemen a ion wi h 500 mg o a s anda dized
amla o mula ion on a ious heal h bioma ke s in heal hy adul s. The s udy demons a ed ha amla in ake led o
signi ican imp o emen s in blood luidi y, a p ima y ma ke o endo helial unc ion, and educ ions in oxida i e s ess
bioma ke s such as on Willeb and Fac o ( WF) and 8-hyd oxy-2-deoxyguanosine (8-OHdG), bo h o which a e
associa ed wi h endo helial dys unc ion and diabe ic asculopa hy. Fu he mo e, as ing glucose le els showed a
s a is ically signi ican educ ion a e ou weeks o supplemen a ion, sugges ing a po en ial glycemic bene i e en in
non-diabe ic indi iduals. This suppo s ea lie p eclinical and clinical e idence ha amla and i s polyphenolic
cons i uen s, pa icula ly ellagi annins and hei gu -de i ed me aboli es such as u oli hins, can imp o e glucose
me abolism, modula e insulin sec e ion, and educe sys emic oxida i e damage, which a e key mechanisms implica ed
in diabe es pa hogenesis. The clinical ansla ion o hese indings, especially when ex ended o a - isk popula ions wi h
p ediabe es could in o m in eg a i e heal hca e models ha blend adi ional nu aceu icals wi h con empo a y
li es yle in e en ions. Ne e heless, he esul s p o ided compelling p elimina y e idence ha amla supplemen a ion
can modula e key isk ac o s and pa hophysiological p ocesses in ol ed in diabe es, making i a aluable adjunc in he
global e o o hal he diabe es epidemic [34].
This s udy also p o ides an explo a ion o Gymnema syl es e, a medicinal plan adi ionally used in Ayu edic
medicine o managing DM. This s udy b idges e hnopha macological knowledge wi h con empo a y biomedical
esea ch, demons a ing ha G. syl es e exe s a b oad spec um o an idiabe ic e ec s. Cen al o i s ac i i y a e
gymnemic acids, a g oup o bioac i e saponins ha no only supp ess he pe cep ion o swee ness, he eby helping
educe suga c a ings, bu also modula e mul iple me abolic pa hways in ol ed in glucose and lipid homeos asis.
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Mechanis ically, gymnemic acids inhibi in es inal glucose abso p ion, s imula e insulin sec e ion, p omo e he
egene a ion o panc ea ic β-cells, and imp o e insulin sensi i i y h ough in e ac ion wi h PPARγ ecep o s. These
ac ions collec i ely con ibu e o lowe ing as ing blood glucose, enhancing glucose up ake in pe iphe al issues, and
educing pos p andial glucose spikes. No ably, ex ac s o G. syl es e ha e also been associa ed wi h β-cell epai in
diabe ic models, suppo ing i s ole no jus in symp om con ol bu in add essing disease pa hogenesis. Fu he mo e,
i s in luence on lipid me abolism indica es a po en ial ole in mi iga ing diabe es-associa ed ca dio ascula isks.
O e all, G. syl es e is a p omising candida e o adjunc he apy in diabe es managemen , wi h po en ial o inspi e he
de elopmen o no el plan -de i ed an idiabe ic agen s [35].
The an idiabe ic po en ial o he me hanolic hea wood ex ac o P e oca pus ma supium (MPME) h ough i s dual
ac ion on oxida i e s ess and glucose up ake in li e -de i ed HepG2 cells was epo ed by Da e al. [36]. Using
ad anced analy ical echniques such as GC–MS, UPLC–MS, and HPTLC, hey iden i ied a ich p o ile o bioac i e phenols,
la onoids, and e penoids, no ably que ce in and epica echin. A concen a ions anging om 23.43 o 93.75 µg/mL,
MPME demons a ed no cy o oxici y while signi ican ly educing oxy adical le els and a enua ing apop osis induced
by high-glucose and H2O2-media ed oxida i e s ess. Impo an ly, ea men wi h 93.75 µg/mL o MPME enhanced
glucose up ake in HepG2 cells, sugges ing imp o ed insulin sensi i i y and glucose me abolism. By mi iga ing eac i e
oxygen species (ROS)-induced cellula damage and p omo ing hepa ic glucose clea ance, MPME ackles c i ical
pa hophysiological ea u es o ype 2 diabe es. These in- i o s udies p o ide a compelling mechanis ic basis o
adi ionally using P. ma supium in diabe es managemen and suppo u he in es iga ion in o i s bioac i e
cons i uen s as na u al he apeu ic agen s [36].
A s udy on Momo dica cha an ia highligh ed s ong e idence o i s suppo i e and he apeu ic e ec s in diabe es
managemen . Nume ous in i o and animal s udies show educed as ing glucose le els, imp o ed insulin sensi i i y,
and be e glycemic con ol wi h bi e melon ex ac s. I con ains cucu bi ane- ype i e penoids (like cha an in and
momo dicosides), la onoids, and polypep ide-p (an insulin-like pep ide). These compounds a e belie ed o exe
an idiabe ic e ec s. Human ials ha e epo ed modes educ ions in blood glucose, hough esul s a e inconsis en [8].
Ano he s udy cha ac e ized he an idiabe ic po en ial o Syzygium cumini ba k decoc ion and a eady- o-se e d ink
h ough phy ochemical p o iling. Employing ac i i y-guided ac iona ion, Thin Laye Ch oma og aphy, and HPLC, he
esea che s alida ed he exis ence o key bioac i e compounds, namely umbelli e one, ellagic acid, and gallic acid,
known o hei an idiabe ic e ec s. These phenolic compounds ha e been shown o imp o e insulin sensi i i y,
egula e glucose me abolism, and inhibi ca bohyd a e-diges ing enzymes. The s udy suppo s he e ec i e use o S.
cumini based p epa a ions in managing hype glycemia and p o ides a scien i ic a ionale o hei inco po a ion in o
diabe es p e en ion and con ol s a egies [37].
Pa il e al. [38] p esen ed a comp ehensi e e alua ion o Azadi ach a indica as a p omising bo anical agen in he
managemen o DM. D awing on a ious in i o and in i o s udies, he a icle ou lined neem’s mul i ace ed mechanisms
which con ibu e o i s an idiabe ic e ec s. A majo inding was neem’s abili y o enhance glucose ole ance and educe
as ing blood glucose le els in diabe ic animal models, sugges ing i s ole in imp o ing insulin sensi i i y. Neem lea and
seed ex ac s also s imula e pe iphe al glucose up ake and egula e essen ial enzymes implica ed in ca bohyd a e
me abolism, including α-glucosidase and α-amylase. Inhibi ing hese enzymes helps o slow ca bohyd a e diges ion and
glucose abso p ion, he eby p e en ing pos p andial blood glucose spikes. Fu he mo e, neem is ich in polyphenols,
la onoids, and limonoids ha exe s ong an ioxidan ac i i y. These compounds help sca enge ee adicals, p o ec
oxida i e s ess-induced damage in panc ea ic β-cells, and imp o e o e all ascula heal h, which a e c i ical ac o s in
p e en ing diabe es complica ions. The e iew also sugges ed neem’s an i-in lamma o y and hepa op o ec i e e ec s,
which may suppo me abolic homeos asis in diabe ic indi iduals. O e all, Azadi ach a indica eme ges as a po en
candida e o adjunc he apy in diabe es managemen , ac ing h ough di e se pa hways including glucose egula ion,
enzyme inhibi ion and oxida i e s ess educ ion. Simila ly, ano he s udy by Ri e a e al. [39] employs an in eg a i e
ne wo k pha macology and molecula docking app oach o unco e he basis o he an ihype glycemic e ec s o
Momo dica cha an ia (bi e melon) and Lage s oemia speciosa (banaba) in T2DM. Using ad anced compu a ional
echniques, he esea che s iden i ied key p o ein a ge s implica ed in T2DM, such as TNF-α, HSP90AA1, MAPK3,
ALDH2, glucokinase (GCK), AKR1B1, ans hy e in (TTR), and e inol-binding p o ein 4 (RBP4), and assessed he
binding a ini y o speci ic phy ochemicals om bi e melon (e.g., cucu bi ane e penoids) and banaba (e.g., decanoic
acid). The a o able docking esul s sugges ha hese bioac i e compounds can engage mul iple diabe es- ele an
a ge s, po en ially exe ing syne gis ic e ec s on pa hways ela ed o in lamma ion, insulin esis ance, me abolic
egula ion, and p o ein s abili y. In pa icula , e penoids om bi e melons demons a e p omising in e ac ions wi h
TNF-α and HSP90AA1, while banaba componen s bind e ec i ely o enzymes like GCK, which plays a cen al ole in
hepa ic glucose me abolism. This mul i- a ge engagemen aligns wi h he he apeu ic need in T2DM o modula e
complex and in e ela ed pa hophysiological p ocesses. Al hough he s udy is compu a ional, i p o ides a s ong
