Hypertension prevalence and vascular aging rise in parallel, driven in part by oxidative stress, endothelial dysfunction, and arterial stiffness.^[1] This further relates to adverse or even fatal cardiovascular events, such as congestive heart failure, stroke as well as myocardial infarction.^[2] It is increasing due to an aging of population and increment in obesity prevelance, and leading to  estimated global burden to affect one third of the world's population in near future. ^[3] likewise many other conditions, HTN too increases with growing age, reported prevalence increased from 27% among young patients below 60 years to 74% among patients above 80 years of age.^[4] Botanical agents with antioxidant and vaso-modulatory actions may complement standard therapy in geriatric care if safe and effective.^[5] Terminalia arjuna (TA), an Ayurvedic cardiotonic, contains polyphenols (e.g., arjunic/arjunolic acids, flavonoids) that demonstrate radical-scavenging, endothelial-supportive, and mild diuretic properties in preclinical work.^[6,7] It has been shown to be cardioprotective, by improving health condition of bloodvessels as well as supportive in controlling blood pressure.^[8] Evidence in older hypertensive adults remains limited, particularly with standardized extracts and rigorous designs. Moreover standard therapies used as anti-hypertensives has been reported to causes adverse drug reactions though the proportion is less approximately 8.69% of total ADRs reported.^[9] We therefore conducted a randomized, double-blind, placebo-controlled trial to assess the effect of TA vs placebo on BP and circulating antioxidant markers over 12 weeks.

Study Design and Oversight

Two-center, randomized 1:1, parallel-group (12 weeks)  trial which is double-blind and placebo-controlled with a 2-week single-blind run-in for adherence assessment. Started with the permission of the institutional ethics committees; after obtaining written informed consent and all the procedures performed following Helsinki declaration.

Enrollment of the Participants

Inclusion: Age ≥65; primary hypertension defined as (a) untreated clinic SBP 140–169 or DBP 90–99 mmHg across two screening visits, or (b) on ≤2 antihypertensives with SBP 130–159 mmHg; ability to complete ambulatory BP monitoring (ABPM).

Exclusion: Secondary hypertension; MI, stroke, or HF hospitalization within 6 months; eGFR <45 mL/min/1.73 m²; ALT/AST >2× ULN; insulin-treated diabetes; chronic inflammatory disease; polyherbal cardiovascular products; anticoagulants beyond low-dose aspirin; allergy to TA.

Randomization and Blinding

Computer-generated permuted blocks (size 4–6), stratified by site and antihypertensive use (yes/no). Allocation concealed via centralized web system. Participants, investigators, and analysts were blinded; capsules identical in appearance and taste.

Interventions

TA group received 500 mg standardized TA extract twice daily with meals (total 1,000 mg/day). Placebo group received inert microcrystalline cellulose capsules. Concomitant antihypertensives were maintained at stable doses unless safety dictated changes (pre-specified protocol for rescue).

Primary Outcome: Change in clinic SBP from baseline to week 12 (average of three seated readings, automated oscillometric device, standardized protocol).

Secondary Outcomes:

• Clinic DBP change (baseline to week 12).
• 24-h ABPM (mean SBP/DBP; daytime/nighttime) at baseline and week 12.
• Antioxidant/oxidative stress biomarkers at baseline and week 12: serum MDA (TBARS method), TAC (Trolox equivalents), SOD activity (pyrogallol auto-oxidation inhibition).
• Safety: labs (CBC, CMP, eGFR), AEs, orthostatic vitals, ECG.

Sample Size

Assuming a between-group SBP difference of 5 mmHg (SD 9), α=0.05, power 0.80, two-sided, 1:1 allocation → 108 participants. Inflating ~10% attrition → target N=120.

Statistical Analysis

Intention-to-treat (all randomized with ≥1 post-baseline measure), last-observation-carried-forward only for safety; primary and secondary efficacy analyzed via ANCOVA with baseline value, site, and antihypertensive use as covariates. Sensitivity analyses included mixed-effects models for repeated measures (MMRM) and per-protocol (≥80% adherence, no rescue meds). Effect sizes reported as adjusted mean differences (aMD) with 95% CIs. Two-sided p<0.05 considered significant. No interim analyses.

Participant Flow

Of 176 screened, 120 randomized (TA 60; placebo 60). Four discontinued (TA 2: relocation n=1, GI upset n=1; placebo 2: non-adherence n=2). 116 completed week 12 assessments.

Baseline Characteristics

Groups were well balanced (Table 1). Mean age 71.8 years; 54% female; 62% on one antihypertensive agent; mean baseline clinic BP 148/88 mmHg; BMI 27.4 kg/m². Biomarkers indicated mild oxidative stress (MDA 3.6 µmol/L).

Table 1. Baseline characteristics (mean ± SD or n [%])

Primary Outcome

At week 12, adjusted mean change in clinic SBP:

• TA: −11.2 mmHg (SE 1.1)
• Placebo: −4.4mmHg (SE 1.1)
  Between-group aMD: −6.8 mmHg (95% CI −9.2 to −4.3; p<0.001).

Secondary Outcomes

• Clinic DBP: TA −5.6 mmHg vs placebo −2.5 mmHg → aMD −3.1 (−4.6 to −1.7), p<0.001.
• 24-h ABPM: SBP aMD −5.1 mmHg (−8.2 to −2.1), p=0.001; DBP aMD −2.6 mmHg (−4.2 to −1.0), p=0.002. Daytime/nighttime patterns mirrored overall effects (no excess nocturnal hypotension).
• Biomarkers:
• MDA: TA −0.72 ± 0.41 vs placebo −0.18 ± 0.39 µmol/L → aMD −0.53 (−0.69 to −0.38), p<0.001.
• TAC: TA +0.24 ± 0.14 vs +0.05 ± 0.13 mM → aMD +0.19 (0.13 to 0.25), p<0.001.
• SOD: TA +2.8 ± 1.6 vs +0.6 ± 1.5 U/mL → aMD +2.1 (1.5 to 2.8), p<0.001.

Table 2. Primary and key secondary endpoints (adjusted analyses)

Subgroups and Sensitivity Analyses

Effect sizes were consistent across age strata (65–74 vs ≥75 years), sex, and baseline antihypertensive use (interaction p>0.10 for all). MMRM yielded similar estimates (SBP aMD −6.5 mmHg; p<0.001). Per-protocol analysis (n=104) showed SBP aMD −7.2 mmHg.

Safety and Tolerability

AEs were mostly mild GI complaints (TA 8.3% vs placebo 6.7%) or transient dizziness (TA 6.7% vs placebo 5.0%). No serious AEs related to product. No between-group differences in orthostatic hypotension, liver enzymes, or eGFR trajectories. One dose reduction in TA arm for dyspepsia; no permanent discontinuations for hypotension.

Raj CD et al^[10] showed the antioxidant effect of T.arjuna extract in his experimental study and Amalraj A Et al^[11]  reviewed its antihypertensive property in detail which further proved to be cardioprotective. Similarly Prakash et al^[12] concluded the hypolipidemic effects of TA in dyslipidemic patients improving lipid profile and improvement in increased blood pressure. Similarly in our study geriatric individuals with hypertension, standardized TA for 12 weeks produced clinically meaningful reductions in clinic and ambulatory BP alongside improvements in oxidative stress markers. The magnitude of SBP reduction (≈7 mmHg vs placebo) aligns with benefits seen with certain lifestyle or adjunctive pharmacologic strategies in older adults and is accompanied by biomarker changes consistent with TA’s proposed antioxidant mechanisms. Improvements in ABPM strengthen internal validity by reducing white-coat effects.

Mechanistic considerations. Shukla SK et al^[13] demonstrated that TA constituents, attenuate lipid peroxidation (lower MDA), and Haque R et al^[14] concluded enhanced enzymatic antioxidant defenses (higher SOD), collectively reducing arterial stiffness and peripheral resistance. Present study also showed the parallel movement of TAC and SOD with BP changes supports—though does not prove—a biological link.

Clinical relevance. Canoy D et al^[15] mentioned in their study that even modest SBP reductions in older adults translate into meaningful decreases in stroke and ischemic events. TA’s tolerability and lack of lab abnormalities are encouraging for real-world integration as an adjunct to standard therapy, pending confirmatory trials.

Limitations. Single botanical and dose; 12-week duration limits inference on durability and hard outcomes. Generalizability beyond relatively healthy ambulatory geriatrics is uncertain. Biomarkers were limited to systemic measures without vascular imaging or flow-mediated dilation. Although adherence was high, unmeasured lifestyle changes cannot be fully excluded.

Future directions. Dose-response and longer studies, inclusion of arterial stiffness, endothelial function, and inflammatory mediators, plus pragmatic trials in polypharmacy contexts and diverse populations.

Standardized Terminalia arjuna (1,000 mg/day) for 12 weeks reduced SBP and DBP and improved antioxidant status in older adults with hypertension with a favorable safety profile. TA may be a promising adjunct in geriatric hypertension management; larger, longer trials are warranted.

We thank the participants and clinic staff. Study product and placebo were manufactured under GMP by a third-party vendor with no role in design, analysis, or manuscript preparation.

Institutional seed grant; no industry funding.

Authors declare no competing interests.

De-identified dataset and analysis code available upon reasonable request to the corresponding author.

1. Herzog MJ, Müller P, Lechner K, et al. Arterial stiffness and vascular aging: mechanisms, prevention, and therapy. Signal Transduct Target Ther. 2025;10(1):282. Published 2025 Sep 1. doi:10.1038/s41392-025-02346-0
2. Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371(9623):1513-1518. doi:10.1016/S0140-6736(08)60655-8
3. Oliveros E, Patel H, Kyung S, et al. Hypertension in older adults: Assessment, management, and challenges. Clin Cardiol. 2020;43(2):99-107. doi:10.1002/clc.23303.
4. Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005;294(4):466-472. doi:10.1001/jama.294.4.466
5. Zhang HP, Zhang DD, Ke Y, Bian K. The Vasodilatory Effects of Anti-Inflammatory Herb Medications: A Comparison Study of Four Botanical Extracts. Evid Based Complement Alternat Med. 2017;2017:1021284. doi:10.1155/2017/1021284
6. Prakash V. Study comparing the hypolipidemic effects of Terminalia arjuna with Rosuvastatin on triglyceride and high density lipoprotein- cholesterol levels. Int J Pharm Chem Anal 2019;6(4):127-35. doi.org/10.18231/j.ijpca.2019.023
7. Prakash V, Goel N, Giri KR, Goel A. Clinical study evaluating antihyperglycemic efficacy and safety of terminalia arjuna versus sitagliptin in Type-2 diabetes mellitus patients. Bioinformation. 2024;20(12):1862-1868. Published 2024 Dec 31. doi:10.6026/9732063002001862
8. Kumar S, Prakash V, Kattimani R, et al Evaluation of cardio-protective effects of a Novel SGLT2 inhibitor beyond glycemic control in preclinical models. 2025;21(8):2459-2463. DOI: 10.6026/973206300212459.
9. Prakash V, Goel N, Yadav AK, Dehade A. COVID-19 pandemic period - adverse drug reactions reporting, observing, assessing and analyzing at tertiary care teaching hospital, IMS-BHU Varanasi – 3-years observational study. Natl J Physiol Pharm Pharmacol. 2024; 14(3): 543-547. doi:10.5455/njppp.2024.14.02072202418022024
10. Raj CD, Shabi MM, Jipnomon J, et al. Terminalia arjuna's antioxidant effect in isolated perfused kidney. Res Pharm Sci. 2012;7(3):181-188.
11. Augustine Amalraj, Sreeraj Gopi, Medicinal properties of Terminalia arjuna (Roxb.) Wight & Arn.: A review, Journal of Traditional and Complementary Medicine, Volume 7, Issue 1,2017,65-78,ISSN2225-4110. doi.org/10.1016/j.jtcme.2016.02.003.
12. Prakash V, Sehgal VK, Bajaj VK, Singh H. To Compare the effects of Terminalia arjuna with Rosuvastatin on Total cholesterol and Low density lipoprotein cholesterol. Int J Med and Dent Sci 2016; 5(1):1056-1066. 10.19056/ijmdsjssmes/2016/v5i1/83576
13. Shukla SK, Sharma SB, Singh UR. Pre-treatment with α-tocopherol and Terminalia arjuna ameliorates, pro-inflammatory cytokines, cardiac and apoptotic markers in myocardial infracted rats. Redox Rep. 2015;20(2):49-59. doi:10.1179/1351000214Y.0000000104
14. Rashedul Haque, Sajib Paul, Md. Tipu Sultan et al , Supplementation of Arjun (Terminalia arjuna) bark powder prevented oxidative stress and enhanced antioxidants in kidneys on isoproterenol-treated Swiss albino mice model, Clinical Nutrition Open Science,Volume 60,2025,66-77, ISSN 2667-2685,doi.org/10.1016/j.nutos.2025.01.013.
15. Canoy, D., Nazarzadeh, M., Copland, E. et al. How Much Lowering of Blood Pressure Is Required to Prevent Cardiovascular Disease in Patients With and Without Previous Cardiovascular Disease?. Curr Cardiol Rep 24, 851–860 (2022). doi.org/10.1007/s11886-022-01706-4