The study, “ Efficacy and Safety of Boldine Combined with Phyllanthus niruri and Ononis spinosa in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Single-Center, Retrospective Cohort Study,” by Ernesto Di Mauro et al. (2024), examined whether three plant-derived components could enhance standard medical expulsive therapy.

With a focus on Phyllanthus niruri kidney–related effects, the authors compared patients treated with tamsulosin alone to those receiving tamsulosin plus boldine, Phyllanthus niruri, and Ononis spinosa. They evaluated stone expulsion rates, time to expulsion, pain control, and safety outcomes using real-world clinical data from a single Italian center, aiming to understand whether this herbal combination could support stone passage without increasing adverse effects.

The authors begin by describing urolithiasis as a common condition that affects people worldwide, with a lifetime prevalence that can reach up to 15 percent. Stones can form for many reasons, including diet, metabolic factors, infections, hereditary tendencies, structural differences in the urinary tract, and environmental influences. According to the paper, about 20 percent of stones are located in the ureter, and roughly 70 percent of those are found in the distal third, the segment closest to the bladder.

They also note that a substantial portion of ureteral stones can pass on their own. The paper states that “approximately 50% of ureteral stones eventually pass spontaneously,” especially when the stones are smaller. This natural tendency to pass spontaneously is part of the reason medical expulsive therapy (MET) is so important. MET aims to increase the chance of passage and reduce the need for surgery.

Medical expulsive therapy (MET) uses medications that relax the ureteral smooth muscle and modify ureteral peristalsis, which can ease stone passage and reduce pain. Tamsulosin, an alpha-1 adrenergic blocker, is highlighted as one of the best-known agents in this setting. The authors point out that tamsulosin “helps to reduce the discomfort associated with stone passage and increases the likelihood of successful stone expulsion.”

Alongside conventional drugs, the paper points to growing interest in plant-based compounds. Phyllanthus niruri, sometimes called the “stonebreaker,” has been studied for possible effects on crystal formation, aggregation, and urinary calcium excretion. Boldine, an alkaloid from Peumus boldus, has antioxidant, anti-inflammatory, and alpha-1 adrenoceptor–blocking properties. Ononis spinosa has a history of use in kidney and bladder conditions and has shown diuretic and other biological activities. The authors explain that these features led to the development of a nutraceutical formulation that combines these three herbal components.

This scientific paper reports on a retrospective cohort study carried out at Humanitas Gavazzeni Hospital in Bergamo, Italy, from March 2023 to December 2023. The researchers included adults aged 18 years or older who had distal ureteral stones located below the sacroiliac joint, with a maximum diameter of 10 millimeters based on urinary ultrasonography or non-contrast computed tomography.

The study used strict inclusion and exclusion criteria. Patients were excluded if they had urinary tract infection, severe refractory pain, hydronephrosis, acute or chronic renal failure, multiple or bilateral ureteral stones, a single functioning kidney, a history of ureteral surgery, or urinary tract anomalies such as horseshoe kidney or duplex systems. Pregnant or breastfeeding women, people with diabetes mellitus, those with hypotension, corticosteroid users, and anyone with known or suspected allergies to the study drugs were also excluded.

After screening 186 patients, the final analysis included 159 participants. They were placed into two groups using chronological criteria.

• Group A received tamsulosin 0.4 mg once daily together with a nutraceutical containing boldine, Phyllanthus niruri, and Ononis spinosa.
• Group B received tamsulosin 0.4 mg alone once daily.

Treatment continued until spontaneous stone passage or for a maximum of 28 days, unless the patient needed active intervention. Follow-up lasted 28 days for the primary evaluation and up to three months overall. Patients were instructed to drink up to 2 liters of water daily and filter their urine to detect stone passage. For pain control, they could use 50 mg sodium diclofenac suppositories as needed.

The primary endpoint was stone expulsion, confirmed by negative ultrasound or CT within the 28-day period. Secondary outcomes included time to expulsion, number of colicky episodes, pain score, amount and duration of nonsteroidal anti-inflammatory drug use, and drug-related adverse effects. Data were analyzed using chi-square tests for categorical variables, and Mann–Whitney U tests for continuous variables, with a p value below 0.05 considered statistically significant.

The combination of boldine, Phyllanthus niruri, and Ononis spinosa with tamsulosin was associated with a higher stone expulsion rate than tamsulosin alone.

• Group A, the combination group, had an expulsion rate of 84.8 percent.
• Group B, the tamsulosin-only group, had an expulsion rate of 52.5 percent.

The authors note that this difference was “statistically significant (p < 0.0001).”

Patients in the combination group also passed their stones more quickly on average.

• Group A had a mean stone expulsion time of 16.33 ± 4.75 days.
• Group B had a mean stone expulsion time of 19.33 ± 6.42 days.

The study reports that patients who received the herbal combination with tamsulosin experienced fewer colicky episodes and needed pain relief for fewer days.

• Analgesic requirement time averaged 2.42 ± 2.56 days in Group A, compared with 6.25 ± 3.05 days in Group B.
• The mean pain score on a 1 to 10 scale was 4.15 ± 1.27 in Group A and 6.91 ± 1.22 in Group B.

Both treatment strategies showed a similar safety profile. Reported side effects included headache, dizziness, nausea, vomiting, postural hypotension, backache, and runny nose. The authors state that “drug-related adverse effects were comparable between the two groups,” and the incidence of these events was low.

1. Need for Surgical Intervention

Some patients still needed surgical intervention when medical therapy did not lead to stone passage. The proportion was smaller in the combination group.

• In Group A, 5 percent of patients ultimately underwent surgery.
• In Group B, 12.6 percent required surgical treatment.

The authors interpret these findings as preliminary evidence that adding boldine, Phyllanthus niruri, and Ononis spinosa to tamsulosin may strengthen medical expulsive therapy for distal ureteral stones. In the discussion, they connect their results to prior work on Phyllanthus niruri and boldine, noting reported effects on ureteral motility, ureteral relaxation, urinary mineral excretion, and crystal behavior.

The study comments that the three herbal extracts “appear to work synergistically to stimulate ureteral contractions and peristalsis, reduce the adhesivity of crystalloids, and promote stone expulsion.”

At the same time, the authors clearly describe the limits of their work. They highlight that this was a retrospective, single-center study with a relatively small sample size. The strict exclusion criteria, while necessary to create a homogeneous group, may limit how broadly the results apply to everyday practice.

Because of these factors, the authors emphasize that their findings should be confirmed in larger, randomized, double-blind, placebo-controlled trials. They suggest that future research could also explore the mechanisms of action of these herbal components in more detail.

Based solely on the authors’ data and analysis, this 2024 scientific paper suggests that combining boldine, Phyllanthus niruri, and Ononis spinosa with tamsulosin may improve several key outcomes in medical expulsive therapy for distal ureteral stones. The combination group had higher stone expulsion rates, shorter expulsion times, fewer colicky episodes, and lower analgesic use, while the pattern of side effects was similar to tamsulosin alone.

The authors present these results as promising but early and stress the need for larger, high-quality clinical trials before firm conclusions can be drawn about the place of this herbal combination in routine care.